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"text": "\n2157\nQuantification of area at risk during coronary occlusion and reperfusion by means of MR perfusion imaging.\n\nSzolar, DH\n\nSaeed, M\n\nWendland, M\n\nSakuma, H\n\nStiskal, MA\n\nDerugin, N\n\nHiggins, CB\n\nBeiträge in Fachzeitschriften\nISI:A1997XM34600001\n9240664.0\nNone\nNone\nPURPOSE: Considerable clinical interest has focused on the size of ischemic myocardium. Fast MR imaging in conjunction with MR contrast media has the potential to identify hypoperfused and infarcted myocardium. This study used MR perfusion imaging to detect and quantify reperfused ischemic myocardium during a brief coronary occlusion and reperfusion, and to characterize the spatial extent of ischemic and reperfused ischemic myocardium relative to the "true" size of the area at risk as defined in histochemical morphometry at post mortem. MATERIAL AND METHODS: The left circumflex (LCX) coronary artery in 8 dogs was occluded for 15 min followed by reperfusion in order to produce regional reversible myocardial ischemia. Perivascular Doppler probes were used to measure blood flow in the left anterior descending (LAD) and LCX coronary arteries. Fast inversion recovery-prepared gradient-recalled-echo images were acquired to delineate the ischemic area during occlusion, and the area of reversible ischemic injury at 1 and 30 min of reperfusion. The size of ischemic and reperfused ischemic myocardium were compared with the area at risk as determined by histochemical morphometry at post mortem. RESULTS: During LCX occlusion, LCX flow decreased from 16+/-1 to 0.2+/-0.1 ml/min. On contrast-enhanced images, ischemic myocardium was evident as a zone of relatively low signal intensity (SI) compared to normal myocardium. The size of the ischemic region was significantly smaller (30+/-2%) than at post mortem (36+/-3%; p<0.05). Immediately after reperfusion, LCX flow increased to 83+/-11 ml/min and the contrast medium caused greater enhancement in the reperfused ischemic region than in the normal myocardium (69+/-3 vs 42+/-3 arbitrary units; p<0.05). The increase in regional SI correlated closely with the increase in regional blood flow (r=0.73). At 1 min of reperfusion, the size of the reperfused ischemic myocardium was larger (48+/-3%, p<0.05) than the area at risk measured at post mortem. At 30 min of reperfusion, when the flow returned to baseline values (16+/-2 ml/min), contrast bolus produced no differential enhancement between the 2 myocardial territories. CONCLUSION: MR perfusion imaging has the potential to detect and quantify the size of ischemic myocardium and the region of post-occlusive hyperemia in the early reperfusion period. There is a significant direct linear relationship between the regional contrast enhancement of reperfused ischemic myocardium and the blood flow during post-occlusive hyperemia. The difference in the size of the area at risk at MR perfusion imaging and at histochemical morphometry may reflect an influence of coronary collateral circulation.\n\n\n"
},
{
"text": "\n133619\nMyocardial infarction as a complication in acute stroke: results from the austrian stroke unit registry.\n\nGattringer, T\n\nNiederkorn, K\n\nSeyfang, L\n\nSeifert-Held, T\n\nSimmet, N\n\nFerrari, J\n\nLang, W\n\nBrainin, M\n\nWilleit, J\n\nFazekas, F\n\nEnzinger, C\n\nBeiträge in Fachzeitschriften\nISI:000332896900011\n24481543.0\n10.1159/000357799\nNone\nPatients with transient ischemic attack (TIA) and stroke have an increased risk for subsequent cardiac events including myocardial infarction (MI), which might be associated with a worse clinical outcome. Rapid identification of stroke patients at higher risk for MI might foster intensified cardiac monitoring or certain therapeutic strategies. However, information regarding acute MI as a complication of stroke in the very acute phase is limited. Moreover, there are no systematic data on the occurrence of MI following intracerebral hematoma. We thus aimed to assess the frequency, clinical characteristics and short-term outcome of patients suffering from acute MI in the stroke unit setting.\n We analyzed 46, 03 patients from 32 Austrian stroke units enrolled in the prospective Austrian Stroke Unit Registry because of TIA/acute stroke over a 6-year period (January 1, 2007 to January 13, 2013). A total of 41, 19 patients (89.3%) had been treated for TIA/ischemic stroke and 4, 84 (10.7%) for primary intracerebral hemorrhage (ICH). Acute MI was defined according to clinical evaluation, ECG findings and laboratory assessments. Patients with evidence for MI preceding the cerebrovascular event were not considered.\n Overall, 421 patients (1%) with TIA/ischemic stroke and 17 patients (0.3%) with ICH suffered from MI during stroke unit treatment for a median duration of 3 days. Patients with TIA/ischemic stroke and MI were significantly older, clinically more severely affected and had more frequently vascular risk factors, atrial fibrillation and previous MI. Total anterior circulation and left hemispheric stroke syndromes were more often observed in MI patients. Patients with MI not only suffered from worse short-term outcome including a higher mortality (14.5 vs. 2%; p < 0.001) at stroke unit discharge, but also acquired more stroke complications like progressive stroke and pneumonia. Multivariate analyses identified previous MI and stroke severity at admission (according to the National Institutes of Health and Stroke Scale score) as factors independently associated with the occurrence of MI on the stroke unit.\n While quite rare in the acute phase after stroke, MI is associated with a poor short-term outcome including a higher mortality. Patients with previous MI and severe stroke syndromes appear to be at particular risk for MI as an early complication in the stroke unit setting. Further studies are needed to determine whether increased vigilance and prolonged (cardiac) monitoring or certain therapeutic approaches could improve the outcome in these high-risk patients.\n\nEnzinger, Christian\n\nFazekas, Franz\n\nGattringer, Thomas\n\nSeifert-Held, Thomas\n\n\n"
},
{
"text": "\n142441\nAllogeneic bone marrow transplantation vs filgrastim-mobilised peripheral blood progenitor cell transplantation in patients with early leukaemia: first results of a randomised multicentre trial of the European Group for Blood and Marrow Transplantation.\n\nSchmitz, N\n\nBacigalupo, A\n\nHasenclever, D\n\nNagler, A\n\nGluckman, E\n\nClark, P\n\nBourquelot, P\n\nGreinix, H\n\nFrickhofen, N\n\nRingdén, O\n\nZander, A\n\nApperley, JF\n\nGorin, C\n\nBorkett, K\n\nSchwab, G\n\nGoebel, M\n\nRussell, NH\n\nGratwohl, A\n\nBeiträge in Fachzeitschriften\nISI:000073631800005\n9632272.0\n10.1038/sj.bmt.1701234\nNone\nIn a multicentre trial involving 20 transplant centres from 10 countries haematopoietic stem cells were obtained either from the bone marrow of 33 sibling donors or from the peripheral blood of 33 such donors after administration of filgrastim (10 microg/kg/day). The haematopoietic stem cells were infused into their HLA-identical recipients suffering from acute leukaemias in remission or chronic myeloid leukaemia in chronic phase. PBPC donors tolerated filgrastim administration and leukapheresis well with the most frequent side-effects being musculoskeletal pain, headache, and mild increases of LDH, AP, Gamma-GT or SGPT. Pain and haematoma at the harvest site and mild anaemia were the most frequent complaints of BM donors. Severe or life-threatening complications were not seen with any type of harvest procedure. Time to platelet recovery greater than 20 x 10(9)/l was 15 days (95% confidence interval (CI) 13-16 days) in the PBPCT group and 19 days (CI 16-25) in the BMT group. Time to neutrophil recovery greater than 0.5 x 10(9)/l was 14 days (CI 12-15 days) in the PBPCT group as compared to 15 days (CI 15-16 days) in the BMT group. The numbers of platelet transfusions administered to PBPCT and BMT patients were 12 (range: 1-28) and 10 (range: 3-39), respectively. Sixteen patients (48%) transplanted with bone marrow and 18 patients (54%) transplanted with PBPC developed acute GVHD of grades II-IV; acute GVHD of grades III or IV developed in six (18%) and seven (21%) patients, respectively. Kaplan-Meier plots for transplant-related mortality until day 100 and leukaemia-free survival at a median of 400 days after BMT or PBPCT showed no significant differences. Administration of filgrastim and leukapheresis in normal donors were feasible and well tolerated. The number of days with restricted activity and of nights spent in hospital was lower in donors of PBPC. Transplantation of PBPC to HLA-identical siblings with early leukaemia resulted in earlier platelet engraftment. The incidence of moderate to severe acute GVHD, transplant-related mortality, and leukaemia-free survival did not show striking differences. Further investigation of allogeneic PBPCT as a substitute for allogeneic BMT is warranted.\n\nGreinix, Hildegard\n\n\n"
},
{
"text": "\n142906\nCervical artery dissection in young adults in the stroke in young Fabry patients (sifap1) study.\n\nvon Sarnowski, B\n\nSchminke, U\n\nGrittner, U\n\nFazekas, F\n\nTanislav, C\n\nKaps, M\n\nTatlisumak, T\n\nPutaala, J\n\nHaeusler, KG\n\nBorges do Amaral E Silva, AD\n\nKinsella, JA\n\nMcCabe, DJ\n\nTobin, WO\n\nHuber, R\n\nWilleit, J\n\nFurtner, M\n\nBodechtel, U\n\nRolfs, A\n\nKessler, C\n\nHennerici, MG\n\nBeiträge in Fachzeitschriften\nISI:000352222400006\n25634656.0\n10.1159/000371338\nNone\nPatients with carotid artery dissection (CAD) have been reported to have different vascular risk factor profiles and clinical outcomes to those with vertebral artery dissection (VAD). However, there are limited data from recent, large international studies comparing risk factors and clinical features in patients with cervical artery dissection (CeAD) with other TIA or ischemic stroke (IS) patients of similar age and sex.\n We analysed demographic, clinical and risk factor profiles in TIA and IS patients ≤55 years of age with and without CeAD in the large European, multi-centre, Stroke In young FAbry Patients 1 (sifap1) study. Patients were further categorised according to age (younger: 18-44 years; middle-aged: 45-55 years), sex, and site of dissection.\n Data on the presence of dissection were available in 4, 08 TIA and IS patients of whom 439 (10.4%) had CeAD: 196 (50.1%) had CAD, 195 (49.9%) had VAD, and 48 had multiple artery dissections or no information regarding the dissected artery. The prevalence of CAD was higher in women than in men (5.9 vs. 3.8%, p < 0.01), whereas the prevalence of VAD was similar in women and men (4.6 vs. 4.7%, n.s.). Patients with VAD were younger than patients with CAD (median = 41 years (IQR = 35-47 years) versus median = 45 years (IQR = 39-49 years); p < 0.01). At stroke onset, about twice as many patients with either CAD (54.0 vs. 23.1%, p < 0.001) or VAD (63.4 vs. 36.6%, p < 0.001) had headache than patients without CeAD and stroke in the anterior or posterior circulation, respectively. Compared to patients without CeAD, hypertension, concomitant cardiovascular diseases and a patent foramen ovale were significantly less prevalent in both CAD and VAD patients, whereas tobacco smoking, physical inactivity, obesity and a family history of cerebrovascular diseases were found less frequently in CAD patients, but not in VAD patients. A history of migraine was observed at a similar frequency in patients with CAD (31%), VAD (27.8%) and in those without CeAD (25.8%).\n We identified clinical features and risk factor profiles that are specific to young patients with CeAD, and to subgroups with either CAD or VAD compared to patients without CeAD. Therefore, our data support the concept that certain vascular risk factors differentially affect the risk of CAD and VAD.\n © 2015 S. Karger AG, Basel.\n\nFazekas, Franz\n\n\n"
},
{
"text": "\n161283\nVisual Acuity Change over 12 Months in the Prospective Progression of Atrophy Secondary to Stargardt Disease (ProgStar) Study: ProgStar Report Number 6.\n\nKong, X\n\nStrauss, RW\n\nCideciyan, AV\n\nMichaelides, M\n\nSahel, JA\n\nMunoz, B\n\nAhmed, M\n\nErvin, AM\n\nWest, SK\n\nCheetham, JK\n\nScholl, HPN\n\nProgStar Study Group\n\nBeiträge in Fachzeitschriften\nISI:000413236000023\n28549516.0\n10.1016/j.ophtha.2017.04.026\nNone\nTo estimate the yearly rate of change of best-corrected visual acuity (BCVA) and the risk of loss 1 line or more over 1 year and to identify risk factors for BCVA loss in patients with Stargardt disease (STGD1).\n Multicenter, prospective cohort study.\n Two hundred fifty-nine patients (489 eyes) with molecularly confirmed STGD1 enrolled at 9 centers in the United States and Europe.\n Participants were followed up every 6 months, and data at the baseline and 6- and 12-month visits were analyzed. Best-corrected visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Standardized reporting forms were used to collect participants' characteristics and clinical observations. Linear mixed effects models were used to estimate the rate of BCVA loss. Linear models with generalized estimating equations were used to identify risk factors for BCVA loss of 1 line or more over 1 year.\n Change in BCVA over 1 year.\n Cross-sectional analysis at baseline showed that earlier symptom onset and longer duration since onset was associated with worse BCVA. Longitudinal analysis showed no overall significant change of BCVA within 12 months, but the rate of BCVA change was significantly different by baseline BCVA (P < 0.001). The BCVA of eyes with baseline BCVA of 20/25 or better declined at a rate of 2.8 ETDRS letters per year (P = 0.10), eyes with baseline BCVA between 20/25 and 20/70 declined at a rate of 2.3 ETDRS letters per year (P = 0.002), eyes with baseline BCVA between 20/70 and 20/200 declined at a rate of 0.8 ETDRS letters per year (P = 0.08), and eyes with baseline BCVA worse than 20/200 showed a significant improvement of 2.3 ETDRS letters per year (P < 0.001). Overall, 12.9% of eyes lost 1 line or more, and the risk of such BCVA loss was different by baseline BCVA level (P = 0.016). Smoking and vitamin A use was not associated significantly with baseline BCVA, nor with rate of BCVA loss over 1 year.\n Change in BCVA in STGD1 patients over a 12-month period was small, but varied depending on baseline BCVA. Given the slow change during 1 year, BCVA is unlikely to be a sensitive outcome measure for STGD1 treatment trials with 1 year's duration.\n Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.\n\nStrauß, Rupert\n\n\n"
},
{
"text": "\n112836\nPostmortem 24-h interval computed tomography findings on intrahepatic gas development and changes of liver parenchyma radiopacity.\n\nFischer, F\n\nGrimm, J\n\nKirchhoff, C\n\nReiser, MF\n\nGraw, M\n\nKirchhoff, S\n\nBeiträge in Fachzeitschriften\nISI:000298634900031\n21862251.0\n10.1016/j.forsciint.2011.07.033\nNone\nPurpose: The purpose of this study was to assess and analyze the development of intrahepatic gas and its distribution over time as well as radiopacity changes of the liver parenchyma after non-traumatic death during a period of 24 h using postmortem computed tomography (PMCT). Materials and methods: Five male corpses (age range 24-64 yrs) who had died for any other reason than trauma were enrolled in this study. Whole body multi detector row computed tomography (MDCT) scans (Brilliance 64-channel, Philips, Amsterdam, NL) were performed for 24 h with one examination per hour. At an average of 6 h after the corpses were found on scene the first CT-exam took place. For the analysis of the intrahepatic gas development and distribution within 24 h after death the liver was virtually divided into four parts. Each examination was analyzed for gas bubbles and the possible increase over time using a semiquantitative/visual assessment employing a four-grade scale. The changes of the radiopacity of the liver parenchyma were assessed in a similar way. In each of the four parts of the liver three regions of interest of the same size were placed and recorded over time. Three radiologists and one coroner independently performed the analysis of the gas development and radiopacity changes. Results: In two corpses the amount of gas and its distribution did not change over the observation period whereas in the other three corpses the gas content increased within the first four to seven hours and was most pronounced in the left liver lobe and least in the right posterior liver lobe. In all five corpses the radiopacity of the liver parenchyma did not change significantly over time with the highest radiopacity in the right posterior liver lobe. Good interobserver reliability concerning the assessment of intrahepatic gas accumulation was found. Discussion: Our results indicate that PMCT is useful to detect intrahepatic gas. However, several reasons for these findings besides putrefaction e. g. trauma, resuscitation exist. For an elucidation of the exact causation of the gas accumulation further studies are required with longer postmortem examination times (24-72 h) to detect more pronounced changes of gas and organ radiopacity but also an earlier start of examination after death is desirable. Moreover, it has to be elucidated whether other organs exhibit a similar behavior and how temperature of the CT-room and the body impacts on these parameters. (C) 2011 Elsevier Ireland Ltd. All rights reserved.\n\n\n"
},
{
"text": "\n123763\nDevelopment and implementation of a mission statement at the University Department of Ophthalmology Graz.\n\nWedrich, A\n\nLangmann, G\n\nKlug, U\n\nLangmann, A\n\nFaschinger, C\n\nWohlfart, C\n\nWeger, M\n\nGranitz, E\n\nKohlhofer, A\n\nHodl, R\n\n\n\nBeiträge in Fachzeitschriften\nISI:000310169100006\nNone\n10.1007/s00717-012-0111-z\nNone\nAn interdisciplinarily generated mission statement facilitates focusing on a corporate goal. This mission statement including vision, mission and values should serve as a basis for a strategy which is supported by all professional groups and which promotes the further development of the organisation unit. The development of such a mission statement is a particular challenge especially in a university setting with its various duties in high level care, science and teaching. Aim of this EFQM (European Foundation of Quality Management) project was the development of a mission statement for our department. The heads of all disciplines in our department were invited to join the project group. In monthly sessions of this project group a mission statement was developed with the help of an external moderator using feedback loops according to the RADAR logic. In the following three months this mission statement was communicated through intensive discussions in the regular meetings of all the various professionals in our department (physicians, nursing teams, laboratory team, administration staff, orthoptic staff, technicians and cleaning staff). Emails, posters and flyers as well as screensavers were used to aid communication. Finally, after designing a questionnaire we performed a survey of a statistically representative group of the department staff by asking 40 % of the members of the various disciplines on a randomly assigned day to answer the questionnaire simultaneously in our lecture hall. For a positive completion of the project, at least 80 % of the respondents had to be able to recognize substantial details of the mission statement. Due to the aforementioned feedback loops the heads of all disciplines were able to define a mission statement including vision, mission and values in a total of five meetings. In the following three meetings the text of the mission statement was completed with graphs and pictures illustrating the content, and the questionnaire was designed. Ninety-eight percent of the questioned staff recognized detailed elements of the mission statement. The acceptance of the mission statement was 80 %. The involvement of all disciplines using joint meetings as well as feedback loops between the meetings enabled the definition and communication of a mission statement of the Department of Ophthalmology of the Medical University of Graz. This mission statement was accepted by 80 % of an interdisciplinarily representative group as a basis for their daily work and for the further development of the organisation.\n\nFaschinger, Christoph\n\nLangmann, Andrea\n\nLangmann, Gerald\n\nWedrich, Andreas\n\nWeger, Martin\n\n\n"
},
{
"text": "\n4309\nEarly statin initiation and outcomes in patients with acute coronary syndromes.\n\nNewby, LK\n\nKristinsson, A\n\nBhapkar, MV\n\nAylward, PE\n\nDimas, AP\n\nKlein, WW\n\nMcGuire, DK\n\nMoliterno, DJ\n\nVerheugt, FW\n\nWeaver, WD\n\nCaliff, RM\n\nSYMPHONY and 2nd SYMPHONY Investigators. Sibrafiban vs Aspirin to Yield Maximun Protection From Ischemic Heart Events Post-acute Coronary Syndromes\n\nBeiträge in Fachzeitschriften\nISI:000176262300023\n12069671.0\n10.1001/jama.287.23.3087\nNone\nCONTEXT: The secondary prevention benefit of therapy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) has been clearly demonstrated; however, the role of early initiation of statins after acute coronary syndromes (ACSs) is unknown. OBJECTIVE: To evaluate the association of early statin initiation (< or = 7 days) after ACS with 90-day and 1-year outcomes. DESIGN: Observational cohort from databases of 2 randomized clinical trials, SYMPHONY and 2nd SYMPHONY. SETTING: Nine hundred thirty-one clinical centers in 37 countries. PATIENTS: A total of 12, 65 ACS patients randomized from August 1997 to August 1999 who were not taking statins prior to the index ACS and who either started statin therapy early (median, 2.0 [interquartile range, 1.0-3.1] days after ACS; n = 3952) or survived more than 5 days after ACS and never received statin therapy (n = 8413). MAIN OUTCOME MEASURES: Ninety-day incidence of death; death or myocardial infarction (MI); and death, MI, or severe recurrent ischemia; as well as 1-year incidence of death. RESULTS: Ninety-day and 1-year unadjusted mortality comparison suggested early statin benefit (1.2% for early statins vs 2.1% for no statins; hazard ratio [HR], 0.58; 95% confidence interval [CI], 0.42-0.81 for 90-day comparisons and 2.3% for early statins vs 4.4% for no statins; HR, 0.52; 95% CI, 0.40-0.68 for 1-year comparison). However, no benefit was evident for 90-day death or MI (6.5% vs 6.9%; HR, 0.95; 95% CI, 0.82-1.11) or death, MI, or severe recurrent ischemia (9.2% vs 8.9%; HR, 1.04; 95% CI, 0.92-1.18). After propensity and covariate adjustment, there were no 90-day or 1-year differences between the early-statin group and the no-statin group. The 90-day adjusted HR for death was 1.08 (95% CI, 0.75-1.56); for death or MI, 1.08 (95% CI, 0.91-1.29); and for death, MI, or severe recurrent ischemia, 1.15 (95% CI, 0.99-1.34). One-year mortality-adjusted HR was 0.99 (95% CI, 0.73-1.33). Among 2711 patients with core laboratory lipid analysis, early statin was associated with higher adjusted risk for death or death or MI at cholesterol levels below treatment guidelines but was more favorable at higher levels. CONCLUSIONS: In this study, there was no relationship between early initiation of statin therapy and improved outcomes although our subset analysis suggests that outcomes after early statin initiation may vary with cholesterol levels. Confirmation of early treatment effects of statins on outcomes awaits the results of adequately powered randomized clinical trials.\n\n\n"
},
{
"text": "\n8795\nA hyperalphalipoproteinaemic family with normal cholesteryl ester transfer/exchange activity.\n\nGroener, JE\n\nda Col, PG\n\nKostner, GM\n\nBeiträge in Fachzeitschriften\nISI:A1987G184000004\n3593240.0\n10.1042/bj2420027\nPMC1147659\nReports of two independent studies suggest that familial hyperalphalipoproteinaemia (FHALP) may be caused by a deficiency of cholesteryl ester transfer/exchange activity (CETP). We also have studied CETP in the plasma of an Italian FHALP kindred. The study group was divided into blood relatives with greater than 1.70 mM high-density-lipoprotein cholesterol (HDL-C) (group I, n = 9), with less than 1.70 mM-HDL-C (group II, n = 12) and in spouses (group III, n = 6). Two different assays were performed to measure CETP activity. In method A the interfering endogenous lipoproteins in the plasma samples were removed by poly(ethylene glycol) precipitation or by ultracentrifugation at a relative density (d) of 1.180. The CETP-activity of these samples was measured in a system consisting of fixed amounts of HDL and cholesteryl [1-14C]oleate-labelled low-density lipoproteins (LDL). In method B, trace amounts of HDL (radiolabelled with cholesteryl [1-14C]oleate) were incubated with plasma for 3 h at 37 degrees C and the distribution of the label among lipoproteins was measured (CET activity). The results can be summarized as follows. The mean CETP activities measured by method A were 187, 213 and 243 nmol/h per ml in groups I, II and III respectively. The proband with the highest HDL-C (4.98 mM) had a CETP activity of 231 nmol/h per ml. The corresponding CET activities measured by method B and expressed as percentage transfer/h were 4.3, 8.0 and 11.2 in groups I-III. The proband with HDL-C = 4.98 mM had a value of only 1.7%/h. There was a strong negative correlation between percentage CE transfer and HDL-C concentration. Calculating these data in terms of CE exchange (nmol/h per ml), groups I, II and III exhibited mean activities of 86, 124 and 110 nmol/h per ml respectively; for the proband this value was 80 nmol/h per ml. Only a slight correlation was found between these values and the HDL-C value. Thus by both methods, (A), measuring the CETP activity per se and (B), measuring the activity in whole plasma (reflecting the activity of the protein and the concentration and composition of lipoproteins), no major differences could be found between the three groups. In our family, therefore, no connection between FHALP and CETP deficiency could be found. It is concluded that, for hyper- and dys-lipoproteinaemic samples, a careful selection of the assay procedure as well as the mode of calculating results is essential. Since this may not hold the previous studies, the supposed connection between FHALP and CETP deficiency is challenged.\n\nKostner, Gerhard\n\n\n"
},
{
"text": "\n159908\nLike or Dislike? Impact of Facebook on Ewing Sarcoma Treatment.\n\nRuckenstuhl, P\n\nSchippinger, M\n\nLiebmann, P\n\nLeithner, A\n\nBernhardt, G\n\nBeiträge in Fachzeitschriften\nISI:000457906300005\n28410188.0\n10.2196/cancer.5367\nPMC5369625\nAn increasing number of patients are raising their voices in online forums to exchange health-related information. Facebook is the leading social media platform with more than 1 billion international daily users recorded in the summer of 2015. Facebook has a dynamic audience and is utilized in a number of ways, discussing medical issues being one of them. Ewing sarcoma mainly affects teenagers and young adults. Additionally, many individuals within this age group are regular users of Facebook. However, little is known about the impact of this modern way of communication via Web-based platforms on patients with Ewing sarcoma and their social environment.\n The aim of this study was to analyze and compare Ewing sarcoma patients' and relatives' behavior on Facebook to draw conclusions regarding the impact of Facebook on Ewing sarcoma treatment.\n We examined a Facebook group named "Ewing Sarcoma Awareness" that is used to exchange information for both patients and relatives regarding Ewing sarcoma. A self-designed questionnaire was used to compare patients' and relatives' answers. Additionally, we analyzed all processes (posts, likes, threads, links) in the group for 6 consecutive months. A total of 65 members of the Facebook group (26 patients, 39 relatives) out of 2227 international group members participated in our study.\n More than 70% (46/65) of all participants reported that they use the group Ewing Sarcoma Awareness as a source of information about Ewing sarcoma. Of the participants, 89% (58/65) agreed on our scale from a little to a lot that being in contact with other affected people through the group makes it easier to handle the diagnosis. In this study, 20% (13/65) of all participants reported that the group affected their choice of treatment and 15% (10/65) of participants were influenced in the selection of their specialist. Regarding the recommendation of the Facebook group toward other people, significant differences (P=.003) were found comparing patients' and relatives' results. During the last 6 months most activities in the group concerned sharing destiny and handling the diagnosis.\n The Facebook group Ewing Sarcoma Awareness has a relevant impact on group members regarding their choice of treatment. Moreover, participants turn toward the group to receive mental and emotional support in everyday life. Statements made within the group are in part questionable from a medical point of view and the impact made by these statements on patients' care requires further evaluation.\n ©Paul Ruckenstuhl, Michael Schippinger, Paul Liebmann, Andreas Leithner, Gerwin Bernhardt. Originally published in JMIR Cancer (http://cancer.jmir.org), 25.08.2016.\n\nBernhardt, Gerwin\n\nLeithner, Andreas\n\nRuckenstuhl, Paul\n\n\n"
},
{
"text": "\n1380\nIntensive care management of acute pancreatitis: recognition of patients at high risk of developing severe or fatal complications.\n\nKaufmann, P\n\nHofmann, G\n\nSmolle, KH\n\nLueger, A\n\nPieber, T\n\nBrunner, G\n\nKrejs, GJ\n\nBeiträge in Fachzeitschriften\nISI:A1996TR42900003\n8677661.0\nNone\nNone\nThe clinical spectrum of acute pancreatitis ranges from mild, self-limiting disease of fulminant illness that may rapidly lead to multiple organ failure and death. To identify factors associated with a subsequent severe course and/or high mortality we investigated retrospectively 91 patients admitted to the medical intensive care unit (ICU) with acute pancreatitis during a 2 year period. 67% of the attacks were mild (< or = 1 complication). The overall mortality rate was 9%, whereby 3% of patients with alcoholic and 13% with biliary pancreatitis died. 75% of the patients in the group with a fatal outcome were aged over sixty and 30% in the group with a mild course (p < 0.05). Females with pancreatitis of biliary origin had a mild course in 57% and a severe (> or = 2 complications) or fatal outcome in 43%. In males with alcohol abuse we observed a mild form of pancreatitis in 79% and a severe or fatal course in 21%. The delay between onset of abdominal pain and commencement of treatment in hospital was greater than 12 hours in 70% of all patients studied and there was no association with severity and development of subsequent complications. The median of the acute physiology and chronic health evaluation scoring system (APACHE-III) on the day of admission was 19 in patients with mild disease, which was significantly lower than in patients with severe (40) or fatal acute pancreatitis (53) (p < 0.0001). Serial APACHE-III measurements over 5 days after admission provided further differentiation between mild and severe or fatal cases (p < 0.0001), but no significant difference was observed between survivors with severe course and fatal outcome. In addition, RANSON scores were calculated for comparison with APACHE-III at admission and after 48 hours: concerning the recognition between mild and severe/fatal pancreatitis both scoring systems exhibited similar significant differences on day 1 and day 2. The RANSON scoring system provided further a significant differentiation between survivors with a severe course of pancreatitis when compared to deaths on day 2, whereas the APACHE-III scoring system did not. Advanced age, female sex, biliary obstruction and elevated RANSON and APACHE-III scores are risk factors for an increased rate of life-threatening complications in acute pancreatitis. The daily assessment of such scoring systems may allow the recognition of such patients and may be helpful in the routine clinical management and monitoring of acute pancreatitis.\n\nBrunner, Gernot\n\nHofmann, Guenter\n\nKrejs, Günter Josef\n\nLueger, Andreas\n\nPieber, Thomas\n\n\n"
},
{
"text": "\n156304\nKLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference.\n\nSchumann, G\n\nLiu, C\n\nO'Reilly, P\n\nGao, H\n\nSong, P\n\nXu, B\n\nRuggeri, B\n\nAmin, N\n\nJia, T\n\nPreis, S\n\nSegura Lepe, M\n\nAkira, S\n\nBarbieri, C\n\nBaumeister, S\n\nCauchi, S\n\nClarke, TK\n\nEnroth, S\n\nFischer, K\n\nHällfors, J\n\nHarris, SE\n\nHieber, S\n\nHofer, E\n\nHottenga, JJ\n\nJohansson, Å\n\nJoshi, PK\n\nKaartinen, N\n\nLaitinen, J\n\nLemaitre, R\n\nLoukola, A\n\nLuan, J\n\nLyytikäinen, LP\n\nMangino, M\n\nManichaikul, A\n\nMbarek, H\n\nMilaneschi, Y\n\nMoayyeri, A\n\nMukamal, K\n\nNelson, C\n\nNettleton, J\n\nPartinen, E\n\nRawal, R\n\nRobino, A\n\nRose, L\n\nSala, C\n\nSatoh, T\n\nSchmidt, R\n\nSchraut, K\n\nScott, R\n\nSmith, AV\n\nStarr, JM\n\nTeumer, A\n\nTrompet, S\n\nUitterlinden, AG\n\nVenturini, C\n\nVergnaud, AC\n\nVerweij, N\n\nVitart, V\n\nVuckovic, D\n\nWedenoja, J\n\nYengo, L\n\nYu, B\n\nZhang, W\n\nZhao, JH\n\nBoomsma, DI\n\nChambers, J\n\nChasman, DI\n\nDaniela, T\n\nde Geus, E\n\nDeary, I\n\nEriksson, JG\n\nEsko, T\n\nEulenburg, V\n\nFranco, OH\n\nFroguel, P\n\nGieger, C\n\nGrabe, HJ\n\nGudnason, V\n\nGyllensten, U\n\nHarris, TB\n\nHartikainen, AL\n\nHeath, AC\n\nHocking, L\n\nHofman, A\n\nHuth, C\n\nJarvelin, MR\n\nJukema, JW\n\nKaprio, J\n\nKooner, JS\n\nKutalik, Z\n\nLahti, J\n\nLangenberg, C\n\nLehtimäki, T\n\nLiu, Y\n\nMadden, PA\n\nMartin, N\n\nMorrison, A\n\nPenninx, B\n\nPirastu, N\n\nPsaty, B\n\nRaitakari, O\n\nRidker, P\n\nRose, R\n\nRotter, JI\n\nSamani, NJ\n\nSchmidt, H\n\nSpector, TD\n\nStott, D\n\nStrachan, D\n\nTzoulaki, I\n\nvan der Harst, P\n\nvan Duijn, CM\n\nMarques-Vidal, P\n\nVollenweider, P\n\nWareham, NJ\n\nWhitfield, JB\n\nWilson, J\n\nWolffenbuttel, B\n\nBakalkin, G\n\nEvangelou, E\n\nLiu, Y\n\nRice, KM\n\nDesrivières, S\n\nKliewer, SA\n\nMangelsdorf, DJ\n\nMüller, CP\n\nLevy, D\n\nElliott, P\n\nBeiträge in Fachzeitschriften\nISI:000389696700064\n27911795.0\n10.1073/pnas.1611243113\nPMC5167198\nExcessive alcohol consumption is a major public health problem worldwide. Although drinking habits are known to be inherited, few genes have been identified that are robustly linked to alcohol drinking. We conducted a genome-wide association metaanalysis and replication study among >105, 00 individuals of European ancestry and identified β-Klotho (KLB) as a locus associated with alcohol consumption (rs11940694; P = 9.2 × 10-12). β-Klotho is an obligate coreceptor for the hormone FGF21, which is secreted from the liver and implicated in macronutrient preference in humans. We show that brain-specific β-Klotho KO mice have an increased alcohol preference and that FGF21 inhibits alcohol drinking by acting on the brain. These data suggest that a liver-brain endocrine axis may play an important role in the regulation of alcohol drinking behavior and provide a unique pharmacologic target for reducing alcohol consumption.\n\nHofer, Edith\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n168141\nSerotonin 1A receptor density measured by F18-Mefway PET/CT in mesiotemporal cortex and raphe does not discriminate therapeutic response in patients with major depressive episode.\n\nBarth, M\n\nDunzinger, A\n\nWimmer, I\n\nWinkler, J\n\nRittmannsberger, H\n\nNader, M\n\nPichler, R\n\nBeiträge in Fachzeitschriften\nISI:000594665600008\n29916219.0\n10.23736/S1824-4785.18.03039-X\nNone\nMore than 50% of patients with major depressive episode (MDE) fail to respond to initial treatment with first line pharmacological therapy. Altered receptor and serotonin transporter function are considered to be associated with mental disorders. Our investigation aimed on the density of the HT1A receptor in mesiotemporal cortex (MTC) and raphe measured by F18-Mefway in patients with MDD.\n Patients with untreated clinically suspected major depressive episode were recruited from June 2012 to May 2014. 49 patients were included into the study: 36 patients (73%) were identified as responders, whereas 13 (27%) were non-responders. Gender distribution was 26 men (56%) and 23 women (44%). For treatment, only a standard medication of a selective serotonin reuptake inhibitor (SSRI) with escitalopram in a range of 10-20 mg/day was permitted. Responders were defined by improvement of the MADRS>50%. Visually MTC had the highest uptake of F18-Mefway among all brain regions, an asymmetry could not be observed in any patient. An elliptical region was drawn over the amygdala and hippocampus area and a small circular region was drawn over the raphe nuclei. All data were calculated related to (unspecific) cerebellar uptake.\n The quotient of the right MTC was 5.00 [4.33; 5.50] in all patients, in responders 5.00 [4.00; 5.75] and in non-responders 5.00 [4.50; 5.50] (P=0.56). The quotient of the left MTC presented with a median level of 4.50 [4.50; 5.50] in all persons. The responders had 4.50 [4.50; 5.75] which was not statistically significant to the data of the non-responders with 5.00 [4.50; 5.50] at P=0.64. The raphe had a median quotient of 2.50 [2.00; 3.00] in all and the cohort of responders, whereas non-responders had 2.50 [2.00; 2.50] (P=0.61). Also the absolute values of SUV in the three brain regions were not statistically different between the cohorts. Additionally, we did not find any sex-related differences in our patient group.\n Serotonin 1A receptor density can be assessed efficiently by F18-Mefway and PET-CT in patients with MDE. The method can be estimated as a possible tool for clinical and academic investigation, marked tracer uptake can constantly be observed at MTC and the raphe. Anyhow, under conditions of real life in patient care, it is not possible to distinguish patients with a good prognosis who will respond to standard SSRI therapy from non-responders who would benefit from a different therapeutic approach starting earlier.\n\n\n"
},
{
"text": "\n152554\nA 9-valent HPV vaccine against infection and intraepithelial neoplasia in women.\n\nJoura, EA\n\nGiuliano, AR\n\nIversen, OE\n\nBouchard, C\n\nMao, C\n\nMehlsen, J\n\nMoreira, ED\n\nNgan, Y\n\nPetersen, LK\n\nLazcano-Ponce, E\n\nPitisuttithum, P\n\nRestrepo, JA\n\nStuart, G\n\nWoelber, L\n\nYang, YC\n\nCuzick, J\n\nGarland, SM\n\nHuh, W\n\nKjaer, SK\n\nBautista, OM\n\nChan, IS\n\nChen, J\n\nGesser, R\n\nMoeller, E\n\nRitter, M\n\nVuocolo, S\n\nLuxembourg, A\n\nBroad Spectrum HPV Vaccine Study\n\nBeiträge in Fachzeitschriften\nISI:000349818700005\n25693011.0\n10.1056/NEJMoa1405044\nNone\nThe investigational 9-valent viruslike particle vaccine against human papillomavirus (HPV) includes the HPV types in the quadrivalent HPV (qHPV) vaccine (6, 11, 16, and 18) and five additional oncogenic types (31, 33, 45, 52, and 58). Here we present the results of a study of the efficacy and immunogenicity of the 9vHPV vaccine in women 16 to 26 years of age.\n We performed a randomized, international, double-blind, phase 2b-3 study of the 9vHPV vaccine in 14, 15 women. Participants received the 9vHPV vaccine or the qHPV vaccine in a series of three intramuscular injections on day 1 and at months 2 and 6. Serum was collected for analysis of antibody responses. Swabs of labial, vulvar, perineal, perianal, endocervical, and ectocervical tissue were obtained and used for HPV DNA testing, and liquid-based cytologic testing (Papanicolaou testing) was performed regularly. Tissue obtained by means of biopsy or as part of definitive therapy (including a loop electrosurgical excision procedure and conization) was tested for HPV.\n The rate of high-grade cervical, vulvar, or vaginal disease irrespective of HPV type (i.e., disease caused by HPV types included in the 9vHPV vaccine and those not included) in the modified intention-to-treat population (which included participants with and those without prevalent infection or disease) was 14.0 per 1000 person-years in both vaccine groups. The rate of high-grade cervical, vulvar, or vaginal disease related to HPV-31, 33, 45, 52, and 58 in a prespecified per-protocol efficacy population (susceptible population) was 0.1 per 1000 person-years in the 9vHPV group and 1.6 per 1000 person-years in the qHPV group (efficacy of the 9vHPV vaccine, 96.7%; 95% confidence interval, 80.9 to 99.8). Antibody responses to HPV-6, 11, 16, and 18 were noninferior to those generated by the qHPV vaccine. Adverse events related to injection site were more common in the 9vHPV group than in the qHPV group.\n The 9vHPV vaccine prevented infection and disease related to HPV-31, 33, 45, 52, and 58 in a susceptible population and generated an antibody response to HPV-6, 11, 16, and 18 that was noninferior to that generated by the qHPV vaccine. The 9vHPV vaccine did not prevent infection and disease related to HPV types beyond the nine types covered by the vaccine. (Funded by Merck; ClinicalTrials.gov number, NCT00543543).\n\nReich, Olaf\n\n\n"
},
{
"text": "\n3325\nStress induced electrolyte and blood gas changes with and without a six days oral treatment with elderberry (Sambucus Nigra L.) concentrate\n\nLeitner, G\n\nWestmoreland, D\n\nKnapp, M\n\nSpencer, K\n\nMerback, J\n\nKuzik, V\n\nWeger, M\n\nPfannhauser, W\n\nPorta, S\n\nBeiträge in Fachzeitschriften\nISI:000089789800004\nNone\nNone\nNone\nElderberry juice has a very high content of phenolic compounds. These phenolic constituents of the elderberry have been the focus of attention in recent studies. By a very delicate process the constituents of the elderberry can be concentrated. In the liquid product the anthocyanins are concentrated eleven- and nine-fold respectively containing 130 000 mg/l of anthocyanines and 30 000 mg/l of catechins. The capsule formula (400 mg dry powder per capsule) contains 140 mg of anthocyanins and 34 mp of catechins each.We investigated the impact of a daily intake of 7 000 mg of anthocyanins and 1 700 mg of catechins on 15 human probands. Their reaction to a standardized bicycle ergometry before and after six days of elderberry concentrate treatment was tested by determination of blood gases, ionized electrolytes, lactate and blood glucose.Basal values before ergometric workload showed significant differences after the elderberry concentrate treatment: pH from 7, 72 to 7, 28 (p = 0.00003), pCO(2) from 40, to 33, (p = 0.000006), HCO3 from 22, 4 to 21, 4 (p = 0.0014), pO(2) from 79 to 65 mmHg (p = 0.0004), O-2 saturation from 94.8 to 92, (p = 0.01). Lactate. blood sugar, calcium and sodium were not significantly different before and after elderberry treatment. However, ionized magnesium was significantly lower after treatment (iMg from 0, 4 to 0, 6 mmol/L, p = 0.0001).The impact of the standardized ergometric workload before and after treatment also resulted in various alterations of the parameters measured: after elderberry treatment O2 sat significantly increased after ergometry (p = 0, 02), magnesium and blood glucose significantly decreased (p = 0.0004 and p = 0, 4, resp.). Lactate delta values were significantly increased after treatment (D = 0, 4). Treatment with elderberry concentrate seems to lead to a considerable increase of metabolism, shown by decreased basal values of pCO(2), increased pH and - interestingly - at the same time decreased pO(2) accompanied by decreased magnesium levels. Thus, tissue seems to take up more oxygen (n spite of increased pH) due to and resulting in increased breathing frequency. This and a more pronounced blood glucose and lactate alteration after ergometry along with a drastic fall in ionized serum magnesium are indicators of a boosted metabolism.We suggest that treatment with anthocyanines and polphenoles is increasing metabolic turnover leading to a magnesium deficient status in the long run. In further investigations the feasibility of an accompanying magnesium substitution to stabilize metabolic effects should be undertaken.\n\nWeger, Martin\n\n\n"
},
{
"text": "\n156760\nPlasma Biomarkers Reflecting Profibrotic Processes in Heart Failure With a Preserved Ejection Fraction: Data From the Prospective Comparison of ARNI With ARB on Management of Heart Failure With Preserved Ejection Fraction Study.\n\nZile, MR\n\nJhund, PS\n\nBaicu, CF\n\nClaggett, BL\n\nPieske, B\n\nVoors, AA\n\nPrescott, MF\n\nShi, V\n\nLefkowitz, M\n\nMcMurray, JJ\n\nSolomon, SD\n\nProspective Comparison of ARNI With ARB on Management of Heart Failure With Preserved Ejection Fraction (PARAMOUNT) Investigators\n\nBeiträge in Fachzeitschriften\nISI:000368622100001\n26754625.0\n10.1161/CIRCHEARTFAILURE.115.002551\nPMC5485256\nHeart failure with preserved ejection fraction is a clinical syndrome that has been associated with changes in the extracellular matrix. The purpose of this study was to determine whether profibrotic biomarkers accurately reflect the presence and severity of disease and underlying pathophysiology and modify response to therapy in patients with heart failure with preserved ejection fraction.\n Four biomarkers, soluble form of ST2 (an interleukin-1 receptor family member), galectin-3, matrix metalloproteinase-2, and collagen III N-terminal propeptide were measured in the Prospective Comparison of ARNI With ARB on Management of Heart Failure With Preserved Ejection Fraction (PARAMOUNT) trial at baseline, 12 and 36 weeks after randomization to valsartan or LCZ696. We examined the relationship between baseline biomarkers, demographic and echocardiographic characteristics, change in primary (change in N-terminal pro B-type natriuretic peptide) and secondary (change in left atrial volume) end points. The median (interquartile range) value for soluble form of ST2 (33 [24.6-48.1] ng/mL) and galectin 3 (17.8 [14.1-22.8] ng/mL) were higher, and for matrix metalloproteinase-2 (188 [155.5-230.6] ng/mL) lower, than in previously published referent controls; collagen III N-terminal propeptide (5.6 [4.3-6.9] ng/mL) was similar to referent control values. All 4 biomarkers correlated with severity of disease as indicated by N-terminal pro B-type natriuretic peptide, E/E', and left atrial volume. Baseline biomarkers did not modify the response to LCZ696 for lowering N-terminal pro B-type natriuretic peptide; however, left atrial volume reduction varied by baseline level of soluble form of ST2 and galectin 3; patients with values less than the observed median (<33 ng/mL soluble form of ST2 and <17.8 ng/mL galectin 3) had reduction in left atrial volume, those above median did not. Although LCZ696 reduced N-terminal pro B-type natriuretic peptide, levels of the other 4 biomarkers were not affected over time.\n In patients with heart failure with preserved ejection fraction, biomarkers that reflect collagen homeostasis correlated with the presence and severity of disease and underlying pathophysiology, and may modify the structural response to treatment.\n URL: http://www.clinicaltrials.gov. Unique identifier: NCT00887588.\n © 2016 American Heart Association, Inc.\n\n\n"
},
{
"text": "\n167167\nAzole-Resistance in <i>Aspergillus terreus</i> and Related Species: An Emerging Problem or a Rare Phenomenon?\n\nZoran, T\n\nSartori, B\n\nSappl, L\n\nAigner, M\n\nSánchez-Reus, F\n\nRezusta, A\n\nChowdhary, A\n\nTaj-Aldeen, SJ\n\nArendrup, MC\n\nOliveri, S\n\nKontoyiannis, DP\n\nAlastruey-Izquierdo, A\n\nLagrou, K\n\nCascio, GL\n\nMeis, JF\n\nBuzina, W\n\nFarina, C\n\nDrogari-Apiranthitou, M\n\nGrancini, A\n\nTortorano, AM\n\nWillinger, B\n\nHamprecht, A\n\nJohnson, E\n\nKlingspor, L\n\nArsic-Arsenijevic, V\n\nCornely, OA\n\nMeletiadis, J\n\nPrammer, W\n\nTullio, V\n\nVehreschild, JJ\n\nTrovato, L\n\nLewis, RE\n\nSegal, E\n\nRath, PM\n\nHamal, P\n\nRodriguez-Iglesias, M\n\nRoilides, E\n\nArikan-Akdagli, S\n\nChakrabarti, A\n\nColombo, AL\n\nFernández, MS\n\nMartin-Gomez, MT\n\nBadali, H\n\nPetrikkos, G\n\nKlimko, N\n\nHeimann, SM\n\nUzun, O\n\nRoudbary, M\n\nde la Fuente, S\n\nHoubraken, J\n\nRisslegger, B\n\nLass-Flörl, C\n\nLackner, M\n\nBeiträge in Fachzeitschriften\nISI:000428531200001\n29643840.0\n10.3389/fmicb.2018.00516\nPMC5882871\nObjectives: Invasive mold infections associated with Aspergillus species are a significant cause of mortality in immunocompromised patients. The most frequently occurring aetiological pathogens are members of the Aspergillus section Fumigati followed by members of the section Terrei. The frequency of Aspergillus terreus and related (cryptic) species in clinical specimens, as well as the percentage of azole-resistant strains remains to be studied. Methods: A global set (n = 498) of A. terreus and phenotypically related isolates was molecularly identified (beta-tubulin), tested for antifungal susceptibility against posaconazole, voriconazole, and itraconazole, and resistant phenotypes were correlated with point mutations in the cyp51A gene. Results: The majority of isolates was identified as A. terreus (86.8%), followed by A. citrinoterreus (8.4%), A. hortai (2.6%), A. alabamensis (1.6%), A. neoafricanus (0.2%), and A. floccosus (0.2%). One isolate failed to match a known Aspergillus sp., but was found most closely related to A. alabamensis. According to EUCAST clinical breakpoints azole resistance was detected in 5.4% of all tested isolates, 6.2% of A. terreus sensu stricto (s.s.) were posaconazole-resistant. Posaconazole resistance differed geographically and ranged from 0% in the Czech Republic, Greece, and Turkey to 13.7% in Germany. In contrast, azole resistance among cryptic species was rare 2 out of 66 isolates and was observed only in one A. citrinoterreus and one A. alabamensis isolate. The most affected amino acid position of the Cyp51A gene correlating with the posaconazole resistant phenotype was M217, which was found in the variation M217T and M217V. Conclusions:Aspergillus terreus was most prevalent, followed by A. citrinoterreus. Posaconazole was the most potent drug against A. terreus, but 5.4% of A. terreus sensu stricto showed resistance against this azole. In Austria, Germany, and the United Kingdom posaconazole-resistance in all A. terreus isolates was higher than 10%, resistance against voriconazole was rare and absent for itraconazole.\n\nBuzina, Walter\n\n\n"
},
{
"text": "\n183247\nA Metabolomics Workflow for Analyzing Complex Biological Samples Using a Combined Method of Untargeted and Target-List Based Approaches.\n\nZüllig, T\n\nZandl-Lang, M\n\nTrötzmüller, M\n\nHartler, J\n\nPlecko, B\n\nKöfeler, HC\n\nBeiträge in Fachzeitschriften\nISI:000579605200001\n32854199.0\n10.3390/metabo10090342\nPMC7570008\nIn the highly dynamic field of metabolomics, we have developed a method for the analysis of hydrophilic metabolites in various biological samples. Therefore, we used hydrophilic interaction chromatography (HILIC) for separation, combined with a high-resolution mass spectrometer (MS) with the aim of separating and analyzing a wide range of compounds. We used 41 reference standards with different chemical properties to develop an optimal chromatographic separation. MS analysis was performed with a set of pooled biological samples human cerebrospinal fluid (CSF), and human plasma. The raw data was processed in a first step with Compound Discoverer 3.1 (CD), a software tool for untargeted metabolomics with the aim to create a list of unknown compounds. In a second step, we combined the results obtained with our internally analyzed reference standard list to process the data along with the Lipid Data Analyzer 2.6 (LDA), a software tool for a targeted approach. In order to demonstrate the advantages of this combined target-list based and untargeted approach, we not only compared the relative standard deviation (%RSD) of the technical replicas of pooled plasma samples (n = 5) and pooled CSF samples (n = 3) with the results from CD, but also with XCMS Online, a well-known software tool for untargeted metabolomics studies. As a result of this study we could demonstrate with our HILIC-MS method that all standards could be either separated by chromatography, including isobaric leucine and isoleucine or with MS by different mass. We also showed that this combined approach benefits from improved precision compared to well-known metabolomics software tools such as CD and XCMS online. Within the pooled plasma samples processed by LDA 68% of the detected compounds had a %RSD of less than 25%, compared to CD and XCMS online (57% and 55%). The improvements of precision in the pooled CSF samples were even more pronounced, 83% had a %RSD of less than 25% compared to CD and XCMS online (28% and 8% compounds detected). Particularly for low concentration samples, this method showed a more precise peak area integration with its 3D algorithm and with the benefits of the LDAs graphical user interface for fast and easy manual curation of peak integration. The here-described method has the advantage that manual curation for larger batch measurements remains minimal due to the target list containing the information obtained by an untargeted approach.\n\nKöfeler, Harald\n\nPlecko, Barbara\n\nTrötzmüller, Martin\n\nZandl-Lang, Martina\n\nZüllig, Thomas\n\n\n"
},
{
"text": "\n566\nConcurrent and independent genetic alterations in the stromal and epithelial cells of mammary carcinoma: implications for tumorigenesis.\n\nMoinfar, F\n\nMan, YG\n\nArnould, L\n\nBratthauer, GL\n\nRatschek, M\n\nTavassoli, FA\n\nBeiträge in Fachzeitschriften\nISI:000086862100041\n10811140.0\nNone\nNone\nThe high frequency of loss of heterozygosity (LOH) in epithelial cells of mammary ductal carcinoma in situ (DCIS) and IDC is a well known phenomenon, whereas the genetic abnormalities in the mammary stroma and its influence on the epithelial component have not been sufficiently studied. Using the PCR, we examined DNA extracts from microdissected stromal and epithelial tissues of 11 breast samples containing DCIS, including five cases associated with IDC. In each case, the mesenchymal tissue consisting of normal-appearing stroma at a distance from DCIS and IDC or stroma close to either DCIS or IDC was manually microdissected. Epithelial cells from morphologically clear-cut normal ducts and lobules, DCIS, and IDC were also microdissected. Twelve polymorphic DNA markers were tested to identify possible genetic alterations in the mesenchymal and epithelial cells on chromosomes 2p, 3p, 11q, 16q, and 17q. Samples from bilateral reduction mammoplasty from 10 women without any clinical, radiological, or pathological abnormalities were also selected as a control (reduction mammoplasty group). Whereas most cases (8/11, 73%) displayed at least one identical LOH in both epithelial and mesenchymal components, LOH at several loci was noted exclusively in stromal cells. The most frequent genetic alterations in the mesenchymal cells were at chromosomes 17q24, 16q23.1-24.2, 3p14.2, and 11q21-23.2, in 87.5, 62, 60, and 45% of informative cases, respectively. The LOH frequency in the stroma close to cancer ranged from 10 to 66.5% for DCIS and from 20 to 75% of informative cases for IDC. Furthermore, 10 of the 12 polymorphic markers revealed LOH in the stroma at a distance, ranging from 11 to 57% of informative cases. None of the control cases (women without any breast disease) revealed LOH either in the epithelial or in the stromal components. Our findings strongly support the concept of stromal-epithelial interaction in the development and progression of mammary neoplasia. Furthermore, this study suggests that genetic alterations in the stromal cells may precede genotypic changes in the epithelial cells. At least in some cases, the mammary stroma in DCIS or IDC apparently represents a neoplastic interactive component rather than a reactive response to the carcinoma. The frequent allelic loss (LOH) in the mammary stroma, identified in our study, may explain some of the fibroblastic abnormalities previously observed in patients with breast carcinoma or a variety of cancer-associated hereditary diseases. We conclude that the mammary stroma may play a key role in inducing neoplastic transformation of epithelial cells, recapitulating its role in normal mammary duct development.\n\nMoinfar, Farid\n\nRatschek, Manfred\n\n\n"
},
{
"text": "\n936\nElevated parathyroid hormone-related peptide levels after human gestation: relationship to changes in bone and mineral metabolism.\n\nDobnig, H\n\nKainer, F\n\nStepan, V\n\nWinter, R\n\nLipp, R\n\nSchaffer, M\n\nKahr, A\n\nNocnik, S\n\nPatterer, G\n\nLeb, G\n\nBeiträge in Fachzeitschriften\nISI:A1995TJ04900052\n8530622.0\n10.1210/jcem.80.12.8530622\nNone\nPTH-related peptide (PTHrP) can be found in high concentrations in human breast milk and has been implicated in material calcium regulation postpartum. We studied the relationship of plasma PTHrP levels of serum markers of bone turnover and selective cancellous bone density in 35 women (age, 25 +/- 3 yr) 2-3 days postpartum and after 3 and 6 months of lactation. The mean postpartum plasma PTHrP levels measured by immunoradiometric assay was 2.64 +/- 0.19 pmol/L (mean +/- SE) and were elevated compared to that in 35 age- and sex-matched controls (1.34 +/- 0.14; P < 0.0001). PTHrP remained significantly elevated, but decreased during the lactation period of 6 +/- 1 months. Immediately postpartum, serum protein levels were lowest, and serum ionized calcium levels highest. At that time, PTH was suppressed to 50% of control values (P < 0.001). Two or 3 days postpartum, serum ionized calcium was negatively correlated with total serum protein (r = -0.47; P < 0.0001) and positively correlated with plasma PTHrP (r = -0.32; P < 0.008). PTH was inversely correlated with ionized calcium (r = -0.24; P = 0.03) and PTHrP (r = -0.31; P < 0.01). Three and 6 months postpartum, serum protein and PTH levels had returned to normal, and ionized calcium concentrations decreased. There was no indication that PTHrP may have any significant systemic effect after 3 and 6 months of lactation. Long term lactation led to a significant decrease in radial cancellous bone density (-4.5%; P < 0.05) at 6 months and to elevations in serum markers of bone resorption (2- to 3-fold for serum carboxy-terminal telopeptide of type I collagen) and formation (1- to 2-fold for osteocalcin and serum carboxy-terminal propeptide of type I procollagen). Bone turnover balance was clearly negative after 3 months of lactation compared to the control value and indicated net bone loss at a time when estrogen levels were low. With ongoing lactation, estrogen levels increased, and bone turnover balance improved significantly and independently of PTHrP levels. We interpret these results as evidence that PTHrP is elevated during the postgestational period and has a weak and temporary effect on calcium metabolism when serum protein levels are reduced. PTHrP does not seem to participate significantly in the regulation of bone turnover during lactation. Normalization of bone turnover balance at 6 months of lactation suggests that further cancellous bone loss is most likely minimal when breast-feeding is extended beyond that time.\n\nLeb, Georg\n\nLipp, Rainer\n\nStepan, Vinzenz\n\n\n"
}
]
}