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"text": "\n80311\nClinical and angiographic risk factors for stroke and death within 30 days after carotid endarterectomy and stent-protected angioplasty: a subanalysis of the SPACE study.\n\nStingele, R\n\nBerger, J\n\nAlfke, K\n\nEckstein, HH\n\nFraedrich, G\n\nAllenberg, J\n\nHartmann, M\n\nRingleb, PA\n\nFiehler, J\n\nSPACE investigators\n\nBruckmann, H\n\nHennerici, M\n\nJansen, O\n\nKlein, G\n\nKunze, A\n\nMarx, P\n\nNiederkorn, K\n\nSchmiedt, W\n\nSolymosi, L\n\nZeumer, H\n\nHacke, W\n\nBeiträge in Fachzeitschriften\nISI:000253580000013\n18242141.0\n10.1016/S1474-4422(08)70024-3\nNone\nCarotid endarterectomy (CEA) and carotid artery stenting (CAS) are used to prevent ischaemic stroke in patients with stenosis of the internal carotid artery. Better knowledge of risk factors could improve assignment of patients to these procedures and reduce overall risk. We aimed to assess the risk of stroke or death associated with CEA and CAS in patients with different risk factors.\n We analysed data from 1196 patients randomised to CAS or CEA in the Stent-Protected Angioplasty versus Carotid Endarterectomy in Symptomatic Patients (SPACE) trial. The primary outcome event was death or ipsilateral stroke (ischaemic or haemorrhagic) with symptoms that lasted more than 24 h between randomisation and 30 days after therapy. Six predefined variables were assessed as potential risk factors for this outcome: age, sex, type of qualifying event, side of intervention, degree of stenosis, and presence of high-grade contralateral stenosis or occlusion. The SPACE trial is registered at Current Controlled Trials, with the international standard randomised controlled trial number ISRCTN57874028.\n Risk of ipsilateral stroke or death increased significantly with age in the CAS group (p=0.001) but not in the CEA group (p=0.534). Classification and regression tree analysis showed that the age that gave the greatest separation between high-risk and low-risk populations who had CAS was 68 years: the rate of primary outcome events was 2.7% (8/293) in patients who were 68 years old or younger and 10.8% (34/314) in older patients. Other variables did not differ between the CEA and CAS groups.\n Of the predefined covariates, only age was significantly associated with the risk of stroke and death. The lower risk after CAS versus CEA in patients up to 68 years of age was not detectable in older patients. This finding should be interpreted with caution because of the drawbacks of post-hoc analyses.\n\nKlein, Guenther\n\n\n"
},
{
"text": "\n110091\nIntegrin-linked kinase, phosphorylated AKT and the prognosis of malignant pleural mesothelioma\n\nWatzka, SB\n\nSetinek, U\n\nStubenberger, EB\n\nTotsch, M\n\nDekan, G\n\nMarcher, M\n\nFleck, T\n\nMuller, MR\n\nBeiträge in Fachzeitschriften\nISI:000287466100007\n20580243.0\n10.1016/j.ejcts.2010.05.007\nNone\nObjective: Integrin-linked kinase (ILK) is a cell membrane-bound molecule implicated in the metastatic progression of many tumour types. It phosphorylates the downstream target AKT (phosphorylated AKT, pAKT), and, by doing this, it activates anti-apoptotic pathways. We have recently shown ILK expression in malignant pleural mesothelioma (MPM). To determine whether ILK expression in MPM is connected with pAKT expression, and whether ILK and pAKT expression have any influence on the patient's prognosis, we correlated ILK and pAKT expression, as assessed by immunohistochemistry, with disease-related survival in a retrospective cohort of 80 MPM patients. Material and methods: The paraffin specimens of 80 MPM cases treated from 1990 to 2006 (52 surgical cases, 28 conservative cases) have been retrieved from the archive. The median (range) patients' age was 62 (28-83 years) years; the male-to-female ratio was 3:1. Fifty percent of the patients had an epitheloid subtype. The samples have been stained with anti-ILK as well as with anti-pAKT and scored by two independent pathologists. Intensity of ILK and pAKTexpression has been correlated with disease-related survival. Results: In total, 73 of 80 (91%) MPM samples expressed ILK; 65 of 74 (88%) MPM samples expressed pAKT. Comparing the 5-year disease-related survival according to ILK or pAKTexpression, no statistically significant difference could be found between ILK and pAKT expressing or non-expressing patients. However, in the subgroup of conservatively treated MPM patients, those with strong ILK expression had a longer 5-year disease-related survival (p < 0.0001). In total, the only prognostic factor across all ILK, pAKT and therapy subgroups was the histological subtype (p = 0.01). The prognostic significance of the histological subtype has been confirmed in multivariate analysis (p = 0.005). Conclusion: The expression of ILK in MPM is connected with the expression of the downstream target pAKT, but neither ILK nor pAKTexpression has a measurable influence on the patient's prognosis, except for certain subgroups of MPM. However, to shed light on the true prognostic impact of ILK and pAKTexpression in MPM, prospective trials are needed. (C) 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.\n\n\n"
},
{
"text": "\n144656\nMorphological MRI characteristics of recent small subcortical infarcts.\n\nGattringer, T\n\nEppinger, S\n\nPinter, D\n\nPirpamer, L\n\nBerghold, A\n\nWünsch, G\n\nRopele, S\n\nWardlaw, JM\n\nEnzinger, C\n\nFazekas, F\n\nBeiträge in Fachzeitschriften\nISI:000363731100019\n25864877.0\n10.1111/ijs.12499\nNone\nNew imaging criteria for recent small subcortical infarcts have recently been proposed, replacing the earlier term 'lacunar infarction', but their applicability and impact on lesion selection is yet unknown.\n To collect information on the morphologic characteristics and variability of recent small subcortical infarcts on magnetic resonance imaging in regard to lesion location and demographic variables.\n We identified all patients with acute stroke and cerebral magnetic resonance imaging from 2008 to 2013 in our hospital database and selected those with a single recent small subcortical infarct defined by an estimated maximal axial diameter of 20 mm. Recent small subcortical infarcts were segmented on diffusion-weighted imaging and fluid-attenuated inversion recovery sequence to calculate the largest axial and longitudinal diameter and lesion volume. We assessed morphometric differences of recent small subcortical infarcts regarding location and demographic variables and the impact of different recent small subcortical infarct definitions on lesion selection.\n Three hundred forty-four patients (median age 72; range 25-92 years, 65% male) were selected. Most recent small subcortical infarcts were located in the basal ganglia (n = 111), followed by pons (n = 92), thalamus (n = 77), and centrum semiovale (n = 64). Quantitative measurements confirmed visual assessment of the axial diameter in 95%. All morphometric variables were strongly intercorrelated and comparable on diffusion-weighted imaging and fluid-attenuated inversion recovery sequence. Recent small subcortical infarcts in the basal ganglia were significantly larger both in the axial and longitudinal direction compared with other regions. Dichotomization of recent small subcortical infarcts according to axial (≤ / >15 mm) or longitudinal (≤ / >20 mm) sizes resulted in different regional frequencies and distributions. Age, gender, and time from stroke onset to magnetic resonance imaging did not influence lesion metrics or the distribution of recent small subcortical infarcts.\n Our study confirms the recent neuroimaging criteria for recent small subcortical infarcts as a practical concept. Definitions of the maximal axial and longitudinal diameter have a significant impact on the frequency and distribution of selected infarcts, which has to be considered for future studies.\n © 2015 World Stroke Organization.\n\nBerghold, Andrea\n\nEnzinger, Christian\n\nEppinger, Sebastian\n\nFazekas, Franz\n\nGattringer, Thomas\n\nPinter, Daniela Theresia\n\nPirpamer, Lukas\n\nRopele, Stefan\n\nWünsch, Gerit\n\n\n"
},
{
"text": "\n162366\nEAACI Guidelines on Allergen Immunotherapy: Allergic rhinoconjunctivitis.\n\nRoberts, G\n\nPfaar, O\n\nAkdis, CA\n\nAnsotegui, IJ\n\nDurham, SR\n\nGerth van Wijk, R\n\nHalken, S\n\nLarenas-Linnemann, D\n\nPawankar, R\n\nPitsios, C\n\nSheikh, A\n\nWorm, M\n\nArasi, S\n\nCalderon, MA\n\nCingi, C\n\nDhami, S\n\nFauquert, JL\n\nHamelmann, E\n\nHellings, P\n\nJacobsen, L\n\nKnol, EF\n\nLin, SY\n\nMaggina, P\n\nMösges, R\n\nOude Elberink, JNG\n\nPajno, GB\n\nPastorello, EA\n\nPenagos, M\n\nRotiroti, G\n\nSchmidt-Weber, CB\n\nTimmermans, F\n\nTsilochristou, O\n\nVarga, EM\n\nWilkinson, JN\n\nWilliams, A\n\nZhang, L\n\nAgache, I\n\nAngier, E\n\nFernandez-Rivas, M\n\nJutel, M\n\nLau, S\n\nvan Ree, R\n\nRyan, D\n\nSturm, GJ\n\nMuraro, A\n\nBeiträge in Fachzeitschriften\nISI:000430164500004\n28940458.0\n10.1111/all.13317\nNone\nAllergic rhinoconjunctivitis (AR) is an allergic disorder of the nose and eyes affecting about a fifth of the general population. Symptoms of AR can be controlled with allergen avoidance measures and pharmacotherapy. However, many patients continue to have ongoing symptoms and an impaired quality of life; pharmacotherapy may also induce some side-effects. Allergen immunotherapy (AIT) represents the only currently available treatment that targets the underlying pathophysiology, and it may have a disease-modifying effect. Either the subcutaneous (SCIT) or sublingual (SLIT) routes may be used. This Guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on AIT for AR and is part of the EAACI presidential project "EAACI Guidelines on Allergen Immunotherapy." It aims to provide evidence-based clinical recommendations and has been informed by a formal systematic review and meta-analysis. Its generation has followed the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included involvement of the full range of stakeholders. In general, broad evidence for the clinical efficacy of AIT for AR exists but a product-specific evaluation of evidence is recommended. In general, SCIT and SLIT are recommended for both seasonal and perennial AR for its short-term benefit. The strongest evidence for long-term benefit is documented for grass AIT (especially for the grass tablets) where long-term benefit is seen. To achieve long-term efficacy, it is recommended that a minimum of 3 years of therapy is used. Many gaps in the evidence base exist, particularly around long-term benefit and use in children.\n © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.\n\nSturm, Gunter\n\nVarga, Eva-Maria\n\n\n"
},
{
"text": "\n183936\nThe Influence of an Attachment-Related Stimulus on Oxytocin Reactivity in Poly-Drug Users Undergoing Maintenance Therapy Compared to Healthy Controls.\n\nFuchshuber, J\n\nTatzer, J\n\nHiebler-Ragger, M\n\nTrinkl, F\n\nKimmerle, A\n\nRinner, A\n\nBuchheim, A\n\nSchrom, S\n\nRinner, B\n\nLeber, K\n\nPieber, T\n\nWeiss, E\n\nLewis, AJ\n\nKapfhammer, HP\n\nUnterrainer, HF\n\nBeiträge in Fachzeitschriften\nISI:000577859800001\n33101071.0\n10.3389/fpsyt.2020.460506\nPMC7544992\nSubstance use disorders (SUDs) have been described as a dysfunctional way to compensate for deficiencies in that person's underlying attachment system. Furthermore, the neuropeptide oxytocin (OT), which is a critical component of the neurobiology of the attachment system, has been shown to effectively reduce addictive behavior and therefore has been discussed as a potential medication in SUD treatment. This study investigates variation in peripheral OT plasma levels as a function of exposure to an attachment-related stimulus in SUD patients compared to healthy controls (HCs).\n A total sample of 48 men, 24 inpatients in maintenance treatment who were diagnosed with poly-drug use disorder (PUD) and 24 HC, was investigated. A 15-min exposure to the Adult Attachment Projective Picture System (AAP) was used as an attachment-related stimulus and coded for attachment status. Blood samples before and after the AAP-assessment were taken and assayed for OT levels. Variation in baselines level of OT was examined in relation to the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST), the Adult Attachment-Scale (AAS), and the Brief Symptom Inventory (BSI).\n Following the AAP stimulus controls showed no significant difference in OT levels elevation from baseline compared to the PUD group's OT levels. Furthermore, in the PUD group only OT-baseline-levels may be negatively associated with the AAS subscale "Comfort with Closeness" and "Anxiety" and lifetime substance use.\n Our results suggest that peripheral OT levels in poly-drug users undergoing maintenance treatment are not significantly different in responsiveness to an attachment related stimulus compared to HC. With regard to non-significant tendencies observed in this study which hint toward decreased OT-reactivity in the PUD group, further research is needed to explore this hypothesis with increased statistical power.\n Copyright © 2020 Fuchshuber, Tatzer, Hiebler-Ragger, Trinkl, Kimmerle, Rinner, Buchheim, Schrom, Rinner, Leber, Pieber, Weiss, Lewis, Kapfhammer and Unterrainer.\n\nKapfhammer, Hans-Peter\n\nLeber, Klaus\n\nPieber, Thomas\n\nRinner, Beate\n\nUnterrainer, Human-Friedrich\n\n\n"
},
{
"text": "\n6782\nSubcutaneous adipose tissue pattern in lean and obese women with polycystic ovary syndrome.\n\nTafeit, E\n\nMöller, R\n\nRackl, S\n\nGiuliani, A\n\nUrdl, W\n\nFreytag, U\n\nCrailsheim, K\n\nSudi, K\n\nHorejsi, R\n\nBeiträge in Fachzeitschriften\nISI:000222319800010\n12773703.0\nNone\nNone\nThe new optical device, Lipometer, permits the noninvasive, quick, safe, and precise measurement of the thickness of subcutaneous adipose tissue (SAT) layers at any given site of the human body. Fifteen anatomically well-defined body sites from neck to calf describe the SAT topography (SAT-Top) like an individual "fingerprint." SAT-Top was examined in 33 women with polycystic ovary syndrome (PCOS), in 87 age-matched healthy controls and in 20 Type-II diabetic women. SAT-Top differences of these three groups were described, and, based on a hierarchical cluster analysis, two distinctly different groups of PCOS women, a lean (PCOS(L)) and an obese (PCOS(O)) cluster, were found. For visual comparison of the different types of body fat distribution, the 15-dimensional body fat information was condensed to a two-dimensional factor plot by factor analysis. For comparison of the PCOS like body fat distribution with the "healthy" fat pattern, the (previously published) SAT-Top results of 590 healthy women and men (20-70 years old) and 162 healthy girls and boys (7-11 years old) were added to the factor plot. PCOS(O) women showed a SAT-Top pattern very similar to that of women with Type-II diabetes, even though the diabetic women were on average 30 years older. Compared with their healthy controls, SAT-Top of these PCOS(O) patients was strongly skewed into the android direction, providing significantly decreased leg SAT development and significantly higher upper body obesity. Compared with healthy women, PCOS(L) patients had significantly lower total SAT development (even though height, weight, and body mass index did not deviate significantly), showing a slightly lowered amount of body fat in the upper region and a highly significant leg SAT reduction. This type of fat pattern is the same as found in girls and boys before developing their sex specific body fat distribution. We conclude that women with PCOS develop an android SAT-Top, but compared in more detail, we found two typical types of body fat distribution: the "childlike" SAT pattern in lean PCOS patients, and the "diabetic" body fat distribution in obese PCOS women.\n\nHorejsi, Renate\n\nTafeit, Erwin\n\n\n"
},
{
"text": "\n62520\nAnesthetics and automaticity in latent pacemaker fibers. IV. Effects of isoflurane and epinephrine or norepinephrine on automaticity of dominant and subsidiary atrial pacemakers in the canine heart.\n\nBoban, M\n\nAtlee, JL\n\nVicenzi, M\n\nKampine, JP\n\nBosnjak, ZJ\n\nBeiträge in Fachzeitschriften\nISI:A1993LV75800021\n8363082.0\n10.1097/00000542-199309000-00020\nNone\nBACKGROUND: Anesthesia and surgery may be associated with atrioventricular junctional or ventricular rhythm disturbances. These may be caused by alteration of automaticity of primary and subsidiary pacemakers. METHODS: The direct effects of isoflurane, alone or in combination with epinephrine (E) and norepinephrine (NE), as well as single effects of E and NE, were examined on automaticity of primary and subsidiary atrial pacemakers (SAP) using a perfused canine right atrial preparation (n = 29). Preparations were perfused with oxygenated Krebs' solution at a constant perfusion pressure of 87 mmHg and a temperature of 36.5 +/- 0.5 degrees C. Delivered concentrations of isoflurane of 1.4 and 2.8% corresponded to measured perfusate concentrations of 315 +/- 7 and 617 +/- 16 microM in experiments with E (n = 14), and 316 +/- 10 and 610 +/- 26 microM in experiments with NE (n = 15). Epinephrine or NE perfusate concentrations were 2 and 5 micrograms/l or 5 and 10 micrograms/l, respectively. To determine the site of earliest activation, extracellular recordings were made from the SA node region and distal sites (approximately 1, 2, and 3 cm) along the sulcus terminalis, the previously reported locations of SAP. Sites of earliest activation shifts from SA node to SAP were scored 1, 2, or 3 depending on the distance from the control pacemaker. The summed shift scores (magnitude score) were normalized by dividing by the total number of preparations for each experimental condition. RESULTS: Exposure to isoflurane, NE, or E alone did not produce a significant increase in the incidence of pacemaker shifts or normalized pacemaker shift scores. Only the high dose of E significantly increased the incidence of pacemaker shifts and normalized shift scores. Dysrhythmogenic potential of E and NE tended to be greater after earlier exposure to isoflurane. Every combination of isoflurane with E or NE produced a significant increase in the incidence of pacemaker shifts and normalized shift scores. CONCLUSIONS: It was concluded that isoflurane with E or NE acts synergistically to increase dysrhythmic potential in the arterial tissue.\n\nVicenzi, Martin\n\n\n"
},
{
"text": "\n65141\nHelical CT of the urinary organs\n\nSchreyer, HH\n\nUggowitzer, MM\n\nRuppert-Kohlmayr, A\n\nBeiträge in Fachzeitschriften\nISI:000174361500011\nNone\n10.1007/s003300101023\nNone\nDespite of the diagnostic potential of conventional CT (CCT), limitations being inherent in this technology reduce its diagnostic confidence and limit clinical CT applications as 3D imagine, Helical CT (HCT) has far overcome the limitations of CCT and has become the standard CT technology. After a short overview on the technique of HCT and its advantages over CCT, the impact of HCT on the detection of disorders of the urinary organs is discussed. Due to the high quality of 3D reconstructions, vessels are visualized free of artefacts resulting in a dramatic improvement and acceptance of CT angiography. which has become a clinically important examination in the evaluation of obstructive renal artery disease. Fast HCT provides a precise assessment of the three phases of the nephrogram and it is a prerequisite for an improved depiction of abnormal vascular perfusion and impaired tubule transit of contrast material. Helical CT enables an improved characterization of cystic mass lesions reducing the diagnosis of indeterminate masses and thus facilitating a better therapeutic management. The diagnosis of renal cell carcinomas (RCC) has improved due to an increased sensitivity in detecting small RCCs, and an increased specificity in the diagnosis of neoplastic lesions. Improved staging of RCCs is the result of accurate assessment of venous tumour extension. When planning nephron-sparing surgery 3D display of the renal tumour helps to determine the resectability of the mass depicting its relation to major renal vessels and the renal collecting system. In the evaluation of renal trauma HCT provides shorter scanning time and thus fewer artefacts in the examination of traumatized patients who cannot cooperate adequately. Three-dimensional postprocessing modalities allow the assessment of the renal vascular pedicel by CT angiography and improve the demonstration of complex lacerations of the renal parenchyma. In the evaluation of the upper urinary tract unenhanced HCT has become the imaging method of choice in the diagnosis and differential diagnosis of acute flank pain since it is highly sensitive and specific in detecting calculus disease. Unenhanced HCT may furthermore demonstrate causes of flank pain unrelated to urolithiasis. Gapless volume scanning and improved resolution in the z-axis during the excretory phase enables improved visualization of the renal collecting systems and ureters, resulting in a better demonstration of intraluminal and extraluminal pathology.\n\n\n"
},
{
"text": "\n118824\nEffects of LF 16-0687 Ms, a bradykinin B(2) receptor antagonist, on brain edema formation and tissue damage in a rat model of temporary focal cerebral ischemia.\n\nZausinger, S\n\nLumenta, DB\n\nPruneau, D\n\nSchmid-Elsaesser, R\n\nPlesnila, N\n\nBaethmann, A\n\nBeiträge in Fachzeitschriften\nISI:000178477600031\n12231253.0\n10.1016/S0006-8993(02)03053-6\nNone\nBradykinin, an endogenous nonapeptide produced by activation of the kallikrein-kinin system, promotes neuronal tissue damage as well as disturbances in blood-brain barrier function through activation of B(2) receptors. LF 16-0687 Ms, a non-peptide competitive bradykinin B(2) receptor antagonist, was recently found to decrease brain swelling in various models of traumatic brain injury. We have investigated the influence of LF 16-0687 Ms on the edema formation, neurological outcome, and infarct size in temporary focal cerebral ischemia in rats. Sprague-Dawley rats were subjected to MCA occlusion for 90 min by an intraluminal filament. Local CBF was bilaterally recorded by laser Doppler flowmetry. Study I: animals were assigned to one of three treatment arms (n=11 each): (a) vehicle, (b) LF 16-0687 Ms (12.0 mg/kg per day), or (c) LF 16-0687 Ms (36.0 mg/kg per day) given repetitively s.c. over 3 days. The neurological recovery was examined daily. The infarct volume was assessed histologically 7 days after ischemia. Study II: brain swelling and bilateral hemispheric water content were determined at 48 h post ischemia in eight rats, subjected to the low dose regimen as described above, and in eight vehicle-treated control animals. All treated animals showed tendency to exhibit improved neurological recovery throughout the observation period as compared to the vehicle-treated controls, while this improvement was only significant within the low dose group from postischemic days 3 to 4. Low dose LF 16-0687 Ms significantly attenuated the total and cortical infarct volume by 50 and 80%, respectively. Furthermore, postischemic swelling (-62%) and increase in water content of the infarcted brain hemisphere (-60.5%) was significantly inhibited. The present findings provide strong evidence for an involvement of bradykinin-mediated secondary brain damage following from focal cerebral ischemia. Accordingly, specific inhibition of bradykinin B(2) receptors by LF 16-0687 Ms attenuated postischemic brain swelling, improved the functional neurological recovery, and limited ischemic tissue damage, raising its potential for clinical evaluation in patients with acute stroke.\n\nLumenta, David Benjamin\n\n\n"
},
{
"text": "\n124608\n3,4-Methylenedioxymethamphetamine induces a hyperthermic and hypermetabolic crisis in pigs with and without a genetic disposition for malignant hyperthermia.\n\nSchutte, JK\n\nSchafer, U\n\nBecker, S\n\nOldewurtel, C\n\nStarosse, A\n\nSingler, P\n\nRichard, A\n\nWappler, F\n\nGerbershagen, MU\n\n\n\nBeiträge in Fachzeitschriften\nISI:000312007800007\n23138574.0\n10.1097/EJA.0b013e32835a1127\nNone\nBackground Clinical symptoms of acute 3, -methylenedioxymethamphetamine (MDMA) intoxication and malignant hyperthermia have many similarities. At present, however, there is contradictory evidence concerning the malignant hyperthermia trigger potency of MDMA. Objective This study was designed to investigate whether MDMA has malignant hyperthermia trigger potential and leads to malignant hyperthermia in pigs with or without a genetic predisposition to the condition. In addition, the therapeutic effectiveness of a new dantrolene sodium suspension was examined. Design Experimental study, using an animal model of Pietrain pigs. Settings Institute for Research in Operative Medicine, University of Witten/Herdecke, Hospital Cologne Merheim, Cologne, Germany, October 2006 to February 2007. Trigger-free anaesthesia was performed on seven malignant hyperthermia-susceptible and six malignant hyperthermia-normal Pietrain pigs, and cumulative doses of MDMA were administered to each animal. Interventions After achieving predefined malignant hyperthermia criteria, standardised therapy was initiated; dantrolene sodium suspension (5 mg kg(-1)) was administered and the injection was repeated after 24 min. Main outcome measures The malignant hyperthermia trigger potency of MDMA was analysed by monitoring pH, PaCO2 and temperature. In addition, concentrations of thyroid hormone, mitochondrial uncoupling protein 3, noradrenaline and free fatty acids during administration of MDMA and dantrolene sodium suspension were analysed. Results MDMA administration led to fulminant hypermetabolic and hyperthermic responses in malignant hyperthermia-susceptible and malignant hyperthermia-normal pigs, with significant decreases inpH(susceptible: pH7.21 +/- 0.11, normal: pH 7.21 +/- 0.07), severe hypercapnia (susceptible: p(a)CO(2) 10.3 +/- 3.5 kPa, normal: p(a)CO(2) 9.8 +/- 1.7 kPa), and hyperthermia (susceptible: 40.6 +/- 2.08 degrees C, normal: 40.1 +/- 0.48 degrees C). Therewere no significant differences in changes in clinical and laboratory variables between groups. The dantrolene therapy regimen was effective in treating the MDMA-induced metabolic crises. Conclusion MDMA is not a classic trigger for the development of malignant hyperthermia reactions in pigs. MDMA intoxication leads to severe, long- lasting hyperthermia and hypermetabolism in both malignant hyperthermia- susceptible and hyperthermianormal pigs, with life-threatening malignant hyperthermia-like symptoms which are responsive to supportive treatment and dantrolene sodium suspension. Eur J Anaesthesiol 2013; 30:29-37\n\nSchäfer, Ute\n\n\n"
},
{
"text": "\n135761\nDisruption of THY-1 signaling in alveolar lipofibroblasts in experimentally induced congenital diaphragmatic hernia.\n\nFriedmacher, F\n\nHofmann, AD\n\nTakahashi, H\n\nTakahashi, T\n\nGosemann, JH\n\nPuri, P\n\nBeiträge in Fachzeitschriften\nISI:000330628000002\n24374733.0\n10.1007/s00383-013-3444-z\nNone\nPulmonary hypoplasia (PH), characterized by alveolar immaturity, remains the main cause of neonatal mortality and long-term morbidity in infants with congenital diaphragmatic hernia (CDH). Lipid-containing interstitial fibroblasts (LIFs) are critically important for normal alveolar development. Thymocyte antigen 1 (Thy-1) is a highly expressed cell-surface protein in this specific subset of lung fibroblasts, which plays a key role in fetal alveolarization by coordinating the differentiation and lipid homeostasis of alveolar LIFs. Thy-1 increases the lipid content of LIFs by upregulation of adipocyte differentiation-related protein (ADRP), a lipogenic molecular marker characterizing pulmonary LIFs. Thy-1 (-/-) mice further show impaired alveolar development with reduced proliferation of pulmonary LIFs, resulting in a PH-similar phenotype. We hypothesized that pulmonary Thy-1 signaling is disrupted in experimentally induced CDH, which may has an adverse effect on the lipid content of alveolar LIFs.\n Timed-pregnant Sprague-Dawley rats were treated with either 100 mg nitrofen or vehicle on embryonic day 9.5 (E9.5). Fetuses were killed on E21.5, and lungs were divided into controls (n = 14) and CDH-associated PH (n = 14). Pulmonary gene expression levels of Thy-1 and ADRP were assessed by quantitative real-time PCR. ADRP immunohistochemistry and oil-red-O staining were used to localize alveolar LIF expression and lipid droplets. Immunofluorescence double staining for Thy-1 and oil-red-O was performed to evaluate Thy-1 expression and lipid content in alveolar LIFs.\n Radial alveolar count was significantly reduced in CDH-associated PH with significant downregulation of pulmonary Thy-1 and ADRP mRNA expression compared to controls. ADRP immunoreactivity and lipid droplets were markedly diminished in alveolar interstitial cells, which coincided with decreased alveolar LIF expression in CDH-associated PH compared to controls. Confocal laser scanning microscopy confirmed markedly decreased Thy-1 expression and lipid content in alveolar LIFs of CDH-associated PH compared to controls.\n Our study provides strong evidence that disruption of pulmonary Thy-1 signaling results in reduced lipid droplets in alveolar LIFs and may thus contribute to PH in the nitrofen-induced CDH model. Treatment modalities aimed at increasing lipid content in alveolar LIFs may therefore have a therapeutic potential in attenuating CDH-associated PH.\n\n\n"
},
{
"text": "\n147779\nInotropic Effects of Experimental Hyperthermia and Hypothermia on Left Ventricular Function in Pigs-Comparison With Dobutamine.\n\nAlogna, A\n\nManninger, M\n\nSchwarzl, M\n\nZirngast, B\n\nSteendijk, P\n\nVerderber, J\n\nZweiker, D\n\nMaechler, H\n\nPieske, BM\n\nPost, H\n\nBeiträge in Fachzeitschriften\nISI:000371530800005\n26474110.0\n10.1097/CCM.0000000000001358\nNone\nThe results from the recent Targeted Temperature Management trial raised the question whether cooling or merely the avoidance of fever mediates better neurologic outcome in resuscitated patients. As temperature per se is a major determinant of cardiac function, we characterized the effects of hyperthermia (40.5°C), normothermia (38.0°C), and mild hypothermia (33.0°C) on left ventricular contractile function in healthy pigs and compared them with dobutamine infusion.\n Animal study.\n Large animal facility, Medical University of Graz, Graz, Austria.\n Nine anesthetized and mechanically ventilated closed-chest Landrace pigs (67 ± 2 kg).\n Core body temperature was controlled using an intravascular device. At each temperature step, IV dobutamine was titrated to double maximum left ventricular dP/dt (1.8 ± 0.1 µg/kg/min at normothermia). Left ventricular pressure-volume relationships were assessed during short aortic occlusions. Left ventricular contractility was assessed by the calculated left ventricular end-systolic volume at an end-systolic left ventricular pressure of 100 mm Hg.\n Heart rate (98 ± 4 vs 89 ± 4 vs 65 ± 2 beats/min; all p < 0.05) and cardiac output (6.7 ± 0.3 vs 6.1 ± 0.3 vs 4.4 ± 0.2 L/min) decreased with cooling from hyperthermia to normothermia and mild hypothermia, whereas left ventricular contractility increased (left ventricular end-systolic volume at a pressure of 100 mm Hg: 74 ± 5 mL at hyperthermia, 52 ± 4 mL at normothermia, and 41 ± 3 mL at mild hypothermia; all p < 0.05). The effect of cooling on left ventricular end-systolic volume at a pressure of 100 mm Hg (hyperthermia to normothermia: -28% ± 3% and normothermia to mild hypothermia: -20% ± 5%) was of comparable effect size as dobutamine at a given temperature (hyperthermia: -28% ± 4%, normothermia: -27% ± 6%, and mild hypothermia: -27% ± 9%).\n Cooling from hyperthermia to normothermia and from normothermia to mild hypothermia increased left ventricular contractility to a similar degree as a significant dose of dobutamine in the normal porcine heart. These data indicate that cooling can reduce the need for positive inotropes and that lower rather than higher temperatures are appropriate for the resuscitated failing heart.\n\nAlbori, Jochen\n\nMächler, Heinrich\n\nManninger-Wünscher, Martin\n\nZirngast, Birgit\n\nZweiker, David\n\n\n"
},
{
"text": "\n174455\nDevelopment and multicentre validation of a prognostic model to predict resectability of pancreatic head malignancy.\n\nGerken, K\n\nRoberts, KJ\n\nReichert, B\n\nSutcliffe, RP\n\nMarcon, F\n\nKamarajah, SK\n\nKaltenborn, A\n\nBecker, T\n\nHeits, NG\n\nMirza, DF\n\nKlempnauer, J\n\nSchrem, H\n\nBeiträge in Fachzeitschriften\nNone\n30263983.0\n10.1002/bjs5.79\nPMC6156170\nAt the time of planned pancreatoduodenectomy patients frequently undergo exploratory laparotomy without resection, leading to delayed systemic therapy. This study aimed to develop and validate a prognostic model for the preoperative prediction of resectability of pancreatic head tumours.\n This was a retrospective study of patients undergoing attempted resection for confirmed malignant tumours of the pancreatic head in a university hospital in Hannover, Germany. The prognostic value of patient and tumour characteristics was investigated in a multivariable logistic regression model. External validation was performed using data from two other centres.\n Some 109 patients were included in the development cohort, with 51 and 175 patients in the two validation cohorts. Eighty patients (73·4 per cent) in the development cohort underwent resection, and 37 (73 per cent) and 141 (80·6 per cent) in the validation cohorts. The main reasons for performing no resection in the development cohort were: local invasion of vasculature or arterial abutment (15 patients, 52 per cent), and liver (12, 41 per cent), peritoneal (8, 28 per cent) and aortocaval lymph node (6, 21 per cent) metastases. The final model contained the following variables: time to surgery (odds ratio (OR) 0·99, 95 per cent c.i. 0·98 to 0·99), carbohydrate antigen 19-9 concentration (OR 0·99, 0·99 to 0·99), jaundice (OR 4·45, 1·21 to 16·36) and back pain (OR 0·02, 0·00 to 0·22), with an area under the receiver operating characteristic (ROC) curve (AUROC) of 0·918 in the development cohort. AUROC values were 0·813 and 0·761 in the validation cohorts. The positive predictive value of the final model for prediction of resectability was 98·0 per cent in the development cohort, and 91·7 and 94·7 per cent in the two external validation cohorts. [Corrections added on 18 July 2018, after first online publication: The figures for OR of the variables time to surgery and CA19-9 in the abstract and in Table 3 and Table 4 were amended from 1·00 to 0·99].\n For preoperative prediction of the likelihood of resectability of pancreatic head tumours, this validated model is a valuable addition to CT findings.\n\nSchrem, Harald Heinrich\n\n\n"
},
{
"text": "\n183128\nObstetrical outcome and treatments in seronegative primary APS: data from European retrospective study.\n\nAbisror, N\n\nNguyen, Y\n\nMarozio, L\n\nEsteve Valverde, E\n\nUdry, S\n\nPleguezuelo, DE\n\nBilloir, P\n\nMayer-Pickel, K\n\nUrbanski, G\n\nZigon, P\n\nDe Moreuil, C\n\nHoxha, A\n\nBezanahary, H\n\nCarbillon, L\n\nKayem, G\n\nBornes, M\n\nYelnik, C\n\nJohanet, C\n\nNicaise-Roland, P\n\nLambert, M\n\nSalle, V\n\nLatino, OJ\n\nHachulla, E\n\nBenedetto, C\n\nBourrienne, MC\n\nBenhamou, Y\n\nAlijotas-Reig, J\n\nFain, O\n\nMekinian, A\n\nEuropean Forum on Antiphospholipid Antibodies\n\nBeiträge in Fachzeitschriften\nISI:000612297500003\n32848089.0\n10.1136/rmdopen-2020-001340\nPMC7507995\nTo compare characteristics, pregnancies and treatments during pregnancies of seronegative and seropositive antiphospholipid syndrome (APS), to analyse factors associated with obstetrical outcome.\n Inclusion criteria were: (1) thrombotic and/or obstetrical APS (Sydney criteria); (2) absence of conventional antiphospholipid antibodies (APL); (3) at least one persistent non-conventional APL among IgA anticardiolipin antibodies, IgA anti-B2GPI, anti-vimentin G/M, anti-annexin V G/M, anti-phosphatidylethanolamine G/M and anti-phosphatidylserine/prothrombin G/M antibodies. The exclusion criteria were: (1) systemic lupus erythematosus ( SLE) or SLE-like disease; and (2) other connective tissue disease.\n A total of 187 women (mean 33±5 years) with seronegative APS were included from 14 centres in Austria, Spain, Italy, Slovenia and France and compared with 285 patients with seropositive APS. Seronegative APS has more obstetrical rather than thrombotic phenotypes, with only 6% of venous thrombosis in comparison to seropositive APS. Cumulative incidence of adverse obstetrical events was similar in seronegative and seropositive APS patients, although higher rates of intrauterine deaths (15% vs 5%; p=0.03), of preeclampsia (7% vs 16%, p=0.048) and lower live birth term (36±3 vs 38±3 weeks of gestation; p=0.04) were noted in seropositive APS. The cumulative incidence of adverse obstetrical events was significantly improved in treated versus untreated seronegative APS (log rank<0.05), whereas there was no difference between patients who received aspirin or aspirin-low-molecular weighted heparin combination.\n Several non-criteria APL can be detected in patients with clinical APS features without any conventional APL, with various rates. The detection of non-criteria APL and thus the diagnosis of seronegative APS could discuss the therapeutic management similar to seropositive APS, but well-designed controlled studies are necessary.\n © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.\n\nMayer-Pickel, Karoline Ilse\n\n\n"
},
{
"text": "\n184234\nCytogenetic and molecular aberrations and worse outcome for male patients in systemic mastocytosis\n\nKluin-Nelemans, HC\n\nJawhar, M\n\nReiter, A\n\nvan Anrooij, B\n\nGotlib, J\n\nHartmann, K\n\nIllerhaus, A\n\nElberink, HNGO\n\nGorska, A\n\nNiedoszytko, M\n\nLange, M\n\nScaffidi, L\n\nZanotti, R\n\nBonadonna, P\n\nPerkins, C\n\nElena, C\n\nMalcovati, L\n\nShoumariyeh, K\n\nvon Bubnoff, N\n\nMuller, S\n\nTriggiani, M\n\nParente, R\n\nSchwaab, J\n\nKundi, M\n\nFortina, AB\n\nCaroppo, F\n\nBrockow, K\n\nZink, A\n\nFuchs, D\n\nAngelova-Fischer, I\n\nYavuz, AS\n\nDoubek, M\n\nMattsson, M\n\nHagglund, H\n\nPanse, J\n\nSimonowski, A\n\nSabato, V\n\nSchug, T\n\nJentzsch, M\n\nBreynaert, C\n\nVarkonyi, J\n\nKennedy, V\n\nHermine, O\n\nRossignol, J\n\nArock, M\n\nValent, P\n\nSperr, WR\n\nBeiträge in Fachzeitschriften\nISI:000582957500019\n33391475.0\n10.7150/thno.51872\nPMC7681091\nIn systemic mastocytosis (SM), the clinical features and survival vary greatly. Patient-related factors determining the outcome in SM are largely unknown. Methods: We examined the impact of sex on the clinical features, progression-free survival (PFS), and overall survival (OS) in 3403 patients with mastocytosis collected in the registry of the European Competence Network on Mastocytosis (ECNM). The impact of cytogenetic and molecular genetic aberrations on sex differences was analyzed in a subset of patients. Results: Of all patients enrolled, 55.3% were females. However, a male predominance was found in a subset of advanced SM (AdvSM) patients, namely SM with an associated hematologic neoplasm (SM-AHN, 70%; p < 0.001). Correspondingly, organomegaly (male: 23% vs. female: 13%, p = 0.007) was more, whereas skin involvement (male: 71% vs. female: 86%, p = 0.001) was less frequent in males. In all patients together, OS (p < 0.0001) was significantly inferior in males, and also within the WHO sub-categories indolent SM, aggressive SM (ASM) and SM-AHN. PFS was significantly (p = 0.0002) worse in males when all patients were grouped together; due to low numbers of events, this significance persisted only in the subcategory smoldering SM. Finally, prognostically relevant cytogenetic abnormalities (10% vs. 5%, p = 0.006) or molecular aberrations (SRSF2/ASXL1/RUNX1 profile; 63% vs. 40%, p = 0.003) were more frequently present in males. Conclusions: Male sex has a major impact on clinical features, disease progression, and survival in mastocytosis. Male patients have an inferior survival, which seems related to the fact that they more frequently develop a multi-mutated AdvSM associated with a high-risk molecular background.\n © The author(s).\n\nSchug, Tanja Daniela\n\n\n"
},
{
"text": "\n187466\nHypomagnesemia Is a Risk Factor for Infections after Kidney Transplantation: A Retrospective Cohort Analysis.\n\nOdler, B\n\nDeak, AT\n\nPregartner, G\n\nRiedl, R\n\nBozic, J\n\nTrummer, C\n\nPrenner, A\n\nSöllinger, L\n\nKrall, M\n\nHöflechner, L\n\nHebesberger, C\n\nBoxler, MS\n\nBerghold, A\n\nSchemmer, P\n\nPilz, S\n\nRosenkranz, AR\n\nBeiträge in Fachzeitschriften\nISI:000643425100001\n33919913.0\n10.3390/nu13041296\nPMC8070921\nMagnesium (Mg2+) deficiency is a common finding in the early phase after kidney transplantation (KT) and has been linked to immune dysfunction and infections. Data on the association of hypomagnesemia and the rate of infections in kidney transplant recipients (KTRs) are sparse.\n We conducted a single-center retrospective cohort study of KTRs transplanted between 2005 and 2015. Laboratory data, including serum Mg2+ (median time of the Mg2+ measurement from KT: 29 days), rate of infections including mainly urinary tract infections (UTI), and common transplant-related viral infections (CMV, polyoma, EBV) in the early phase after KT were recorded. The primary outcome was the incidence of infections within one year after KT, while secondary outcomes were hospitalization due to infection, incidence rates of long-term (up to two years) infections, and all-cause mortality.\n We enrolled 376 KTRs of whom 229 patients (60.9%) suffered from Mg2+ deficiency defined as a serum Mg2+ < 0.7 mmol/L. A significantly higher incidence rate of UTIs and viral infections was observed in patients with versus without Mg2+ deficiency during the first year after KT (58.5% vs. 47.6%, p = 0.039 and 69.9% vs. 51.7%, p < 0.001). After adjustment for potential confounders, serum Mg2+ deficiency remained an independent predictor of both UTIs and viral infections (odds ratio (OR): 1.73, 95% CI: 1.04-2.86, p = 0.035 and OR: 2.05, 95% CI: 1.23-3.41, p = 0.006). No group differences according to Mg2+ status in hospitalizations due to infections and infection incidence rates in the 12-24 months post-transplant were observed. In the Cox regression analysis, Mg2+ deficiency was not significantly associated with all-cause mortality (HR: 1.15, 95% CI: 0.70-1.89, p = 0.577).\n KTRs suffering from Mg2+ deficiency are at increased risk of UTIs and viral infections in the first year after KT. Interventional studies investigating the effect of Mg2+ supplementation on Mg2+ deficiency and viral infections in KTRs are needed.\n\nBerghold, Andrea\n\nDeak, Andras Tamas\n\nGoritschan, Anna\n\nHebesberger, Carina Sarah\n\nKrall, Marcell\n\nOdler, Balazs\n\nPilz, Stefan\n\nPregartner, Gudrun\n\nRiedl, Regina\n\nRosenkranz, Alexander\n\nSchemmer, Peter\n\nTrummer, Christian\n\n\n"
},
{
"text": "\n395\nCarcinoma of the cervix: analysis of complications after primary external beam radiation and Ir-192 HDR brachytherapy.\n\nKapp, KS\n\nStuecklschweiger, GF\n\nKapp, DS\n\nPoschauko, J\n\nPickel, H\n\nHackl, A\n\nBeiträge in Fachzeitschriften\nISI:A1997WR94000005\n9106923.0\n10.1016/s0167-8140(96)01881-6\nNone\nThere is still a concern that the use of HDR brachytherapy might result in an increase of late tissue damage. This restrospective study evaluates the incidence and severity of late complications in patients with carcinoma of the cervix who underwent combined external beam radiation (EBR) and Ir-192 HDR brachytherapy and attempts to identify pretreatment and treatment parameters correlating with late complications.\n Between 1985 and 1992, 161 patients with carcinoma of the cervix (FIGO stages IB-IVB) received EBR to the pelvis (ave, max. dose 48.8 Gy) followed by 1-6 Ir-192 HDR placements (median 2). Doses to point A ranged from 8.5 to 38.7 Gy (median 17 Gy). Parameters examined included age, diabetes, obesity, history of inflammatory bowel disease or diverticulitis, prior surgery, hemoglobin level, FIGO stage, EBR dose, technique and daily dose fraction, number of HDR treatments and total dose to point A, maximum doses to bladder and rectum delivered by brachytherapy and cumulative dose to point A. Median follow-up for all patients was 37 months. Complications were rated using an in-house scoring system and according to the French-Italian Glossary (FIG).\n Actuarial 5-year survival was 93%, 57%, 46%, and 0% for stages IB, II, IIIB, and IV, respectively. Of 161 patients, 11% developed moderate and 3.7% severe sequelae (FIG: 2.5%, 3.7%). Since some patients experienced more than one complication, the overall incidence was 13.6% and 4.9% (FIG: 3.1%, 4.9%) with respective 5-year actuarial rates of 14% and 5% for moderate, and 2% and 8% for severe bowel and genitourinary tract complications (FIG: 3.5%, 0, and 2%, 8%). All severe bowel complications occurred within 1.5 years whereas urinary tract sequelae continued to develop throughout the follow-up period. FIGO stage was associated with a significant increase in late sequelae (P = 0.015). Analysis of the remaining pretreatment and treatment parameters failed to reveal any statistically significant correlation with moderate or severe sequelae.\n In our series using HDR brachytherapy, complication and survival rates were comparable with other series employing either LDR or HDR procedures. Of all parameters analysed, stage of disease was the only parameter significantly correlated with complications in univariate and multivariate analysis.\n\n\n"
},
{
"text": "\n121377\nLow-Gradient Aortic Valve Stenosis Myocardial Fibrosis and Its Influence on Function and Outcome\n\nHerrmann, S\n\nStork, S\n\nNiemann, M\n\nLange, V\n\nStrotmann, JM\n\nFrantz, S\n\nBeer, M\n\nGattenlohner, S\n\nVoelker, W\n\nErtl, G\n\nWeidemann, F\n\nBeiträge in Fachzeitschriften\nISI:000292681600010\n21757118.0\n10.1016/j.jacc.2011.02.059\nNone\nObjectives This prospective cohort study in patients with aortic stenosis (AS) aimed to identify surrogates of myocardial fibrosis that are easy to derive in clinical practice, allow the differentiation of low-gradient severe AS from moderate AS, and have an impact on clinical outcome. Background In patients with symptomatic aortic AS, a characteristic subgroup (i.e., up to one-third) exhibits severe AS with a concomitant low mean valve gradient either with preserved or reduced ejection fraction (EF). It is hypothesized that these patients tend to have an advanced stage of myocardial fibrosis and poor clinical outcome. Methods Eighty-six patients with moderate or severe AS were examined by echocardiography including conventional aortic valve assessment, mitral ring displacement, and strain-rate imaging. Replacement fibrosis was quantified by late-enhancement magnetic resonance imaging. Biopsy samples were taken from patients with severe AS (n = 69) at aortic valve replacement. All patients were followed for 9 months. Results Patients were divided into 4 groups according to aortic valve area (<1.0 cm(2)), mean valve gradient >= 40 mm Hg, and EF (<50%): group 1, moderate AS (n = 17); group 2, severe AS/high gradient (n = 49); group 3, severe AS/low gradient/preserved EF (n = 11); and group 4, severe AS/low gradient/decreased EF (n = 9). At baseline, a significant decrease in mitral ring displacement and systolic strain rate was detected in patients with low-gradient AS. In low-gradient groups, a higher degree of interstitial fibrosis in biopsy samples and more late-enhancement magnetic resonance imaging segments were observed. A close inverse correlation was found between interstitial fibrosis and mitral ring displacement (r = -0.79, p < 0.0001). Clinical outcome was best for patients in group 1, whereas mortality risk increased substantially in groups 2 through 4. Conclusions In severe AS, a low gradient is associated with a higher degree of fibrosis, decreased longitudinal function, and poorer clinical outcome despite preserved EF. Mitral ring displacement differentiates between moderate AS and low-gradient/severe AS with preserved EF. (J Am Coll Cardiol 2011;58:402-12) (C) 2011 by the American College of Cardiology Foundation\n\n\n"
},
{
"text": "\n146897\nAdhesive strength of bone-implant interfaces and in-vivo degradation of PHB composites for load-bearing applications.\n\nMeischel, M\n\nEichler, J\n\nMartinelli, E\n\nKarr, U\n\nWeigel, J\n\nSchmöller, G\n\nTschegg, EK\n\nFischerauer, S\n\nWeinberg, AM\n\nStanzl-Tschegg, SE\n\nBeiträge in Fachzeitschriften\nISI:000366226500010\n26318571.0\n10.1016/j.jmbbm.2015.08.004\nNone\nAim of this study was to evaluate the response of bone to novel biodegradable polymeric composite implants in the femora of growing rats. Longitudinal observation of bone reaction at the implant site (BV/TV) as well as resorption of the implanted pins were monitored using in vivo micro-focus computed tomography (µCT). After 12, 24 and 36 weeks femora containing the implants were explanted, scanned with high resolution ex vivo µCT, and the surface roughness of the implants was measured to conclude on the ingrowth capability for bone tissue. Scanning electron microscope (SEM) and energy dispersive X-ray spectroscopy (EDX) were used to observe changes on the surface of Polyhydroxybutyrate (PHB) during degradation and cell ingrowth. Four different composites with zirconium dioxide (ZrO2) and Herafill(®) were compared. After 36 weeks in vivo, none of the implants did show significant degradation. The PHB composite with ZrO2 and a high percentage (30%) of Herafill® as well as the Mg-alloy WZ21 showed the highest values of bone accumulation (increased BV/TV) around the implant. The lowest value was measured in PHB with 3% ZrO2 containing no Herafill®. Roughness measurements as well as EDX and SEM imaging could not reveal any changes on the PHB composites׳ surfaces. Biomechanical parameters, such as the adhesion strength between bone and implant were determined by measuring the shear strength as well as push-out energy of the bone-implant interface. The results showed that improvement of these mechanical properties of the studied PHBs P3Z, P3Z10H and P3Z30H is necessary in order to obtain appropriate load-bearing material. The moduli of elasticity, tensile strength and strain properties of the PHB composites are close to that of bone and thus promising. Compared to clinically used PLGA, PGA and PLA materials, their additional benefit is an unchanged local pH value during degradation, which makes them well tolerated by cells and immune system. They might be used successfully for personalized 3D printed implants or as coatings of rapidly dissolving implants. \n Copyright © 2015 Elsevier Ltd. All rights reserved.\n\nFischerauer, Stefan Franz\n\nWeinberg, Annelie-Martina\n\n\n"
},
{
"text": "\n155968\nImmunodominance and functional alterations of tumor-associated antigen-specific CD8+ T-cell responses in hepatocellular carcinoma.\n\nFlecken, T\n\nSchmidt, N\n\nHild, S\n\nGostick, E\n\nDrognitz, O\n\nZeiser, R\n\nSchemmer, P\n\nBruns, H\n\nEiermann, T\n\nPrice, DA\n\nBlum, HE\n\nNeumann-Haefelin, C\n\nThimme, R\n\nBeiträge in Fachzeitschriften\nISI:000333249800025\n24002931.0\n10.1002/hep.26731\nPMC4139003\nHepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide with a poor prognosis and limited therapeutic options. To aid the development of novel immunological interventions, we studied the breadth, frequency, and tumor-infiltration of naturally occurring CD8(+) T-cell responses targeting several tumor-associated antigens (TAA). We used overlapping peptides spanning the entire alpha-fetoprotein (AFP), glypican-3 (GPC-3), melanoma-associated gene-A1 (MAGE-A1) and New York-esophageal squamous cell carcinoma-1 (NY-ESO-1) proteins and major-histocompatibility-complex-class-I-tetramers specific for epitopes of MAGE-A1 and NY-ESO-1 to analyze TAA-specific CD8(+) T-cell responses in a large cohort of HCC patients. After nonspecific expansion in vitro, we detected interferon-γ (IFN-γ)-producing CD8(+) T cells specific for all four TAA in the periphery as well as in liver and tumor tissue. These CD8(+) T-cell responses displayed clear immunodominance patterns within each TAA, but no consistent hierarchy was observed between different TAA. Importantly, the response breadth was highest in early-stage HCC and associated with patient survival. After antigen-specific expansion, TAA-specific CD8(+) T cells were detectable by tetramer staining but impaired in their ability to produce IFN-γ. Furthermore, regulatory T cells (Treg) were increased in HCC lesions. Depletion of Treg from cultures improved TAA-specific CD8(+) T-cell proliferation but did not restore IFN-γ-production.\n Naturally occurring TAA-specific CD8(+) T-cell responses are present in patients with HCC and therefore constitute part of the normal T-cell repertoire. Moreover, the presence of these responses correlates with patient survival. However, the observation of impaired IFN-γ production suggests that the efficacy of such responses is functionally limited. These findings support the development of strategies that aim to enhance the total TAA-specific CD8(+) T-cell response by therapeutic boosting and/or specificity diversification. However, further research will be required to help unlock the full potential of TAA-specific CD8(+) T-cell responses.\n © 2014 The Authors. Hepatology published by Wiley on behalf of the American Association for the Study of Liver Diseases.\n\nSchemmer, Peter\n\n\n"
}
]
}