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"text": "\n3068\nDelayed insulin transport across endothelium in insulin-resistant JCR:LA-cp rats.\n\nWascher, TC\n\nWölkart, G\n\nRussell, JC\n\nBrunner, F\n\nBeiträge in Fachzeitschriften\nISI:000086987600019\n10905490.0\n10.2337/diabetes.49.5.803\nNone\nCapillary endothelial cells are thought to limit the transport of insulin across the endothelium, resulting in attenuated insulin action at target sites. Whether endothelial insulin transport is altered in dysglycemic insulin-resistant states is not clear and was therefore investigated in the JCR:LA-cp corpulent male rat, which exhibits the metabolic syndrome of obesity, insulin resistance, hyperlipidemia, and hyperinsulinemia. Lean littermates that did not develop these alterations served as controls. Animals of both groups were normotensive (mean arterial pressure 136+/-2 mmHg). Hearts from obese and lean rats aged 7 (n = 6) or 18 (n = 8) weeks were perfused in vitro at 10 ml/min per gram wet wt over 51 min with Krebs-Henseleit buffer containing 0.1 or 0.5 U human insulin/l (equivalent to 0.6 and 3 nmol/l). Interstitial fluid was collected using a validated method, and interstitial insulin was determined with a radioimmunoassay. At 0.1 U/l, insulin transfer velocity was similar in both experimental groups (half-times of transfer: 11+/-0.2 min in obese and 18+/-4 min in lean rats; NS), but at 0.5 U/l, the respective half-times were 7+/-1 min in lean and 13+/-2 min in obese rats (P < 0.05). The steady-state level of insulin in the interstitium was 34+/-1% of the vascular level at 0.1 U/l and reached the vascular level (102+/-2%) at 0.5 U/l in both lean and obese rats. In rats aged 18 weeks, the half-times of insulin transfer were 31+/-2 and 14+/-l min in obese rats and 10+/-0.3 and 7+/-0.3 min in lean rats (P < 0.05). Again, interstitial steady-state levels were similar in both groups. Finally, postprandial insulin dynamics were simulated over a period of 120 min with a peak concentration of 0.8 U/l in rats aged 27 weeks (n = 4). The maximal interstitial level was 0.38+/-0.02 U/l in lean rats and 0.24+/-0.02 U/l in obese rats (P < 0.05), and a similar difference was noted throughout insulin infusion (areas under the transudate concentration-time curves: 17 and 11 U/min per 1, respectively). These data show, for the first time in a genetic animal model of insulin resistance, that transfer of insulin across the endothelium is substantially delayed in obese insulin-resistant rats and that it likely contributes to the postprandial alterations of glucose metabolism observed in the metabolic syndrome.\n\n\n"
},
{
"text": "\n3165\nIntestinal elimination of hydroxyethyl starch?\n\nLenz, K\n\nSchimetta, W\n\nPölz, W\n\nKröll, W\n\nGruy-Kapral, C\n\nMagometschnigg, D\n\nBeiträge in Fachzeitschriften\nISI:000088208300014\n10945391.0\n10.1007%2Fs001340051240\nNone\nOBJECTIVE: Hydroxyethyl starch (HES) is mainly eliminated via the kidneys. Any information about extrarenal elimination obtained so far has been either incomplete or contradictory. The objective of this study was to quantify the intestinal excretion of infused HES with a mean molecular weight of 200, 00 and a molar substitution of 0.5 (HES 200/0.5) and to compare the reappearance/recovery rate in urine and plasma. DESIGN: Prospective clinical study without control group. SETTING: The study was conducted at the Institute of Hypertension of the Society of Clinical Pharmacology, Vienna, Austria, which is an establishment for research in volunteers. PARTICIPANTS: The results of six out of seven healthy male volunteers were appropriate for analysis. One trial subject had to be excluded from the study because of severe protocol violation (mixing of stool and urine samples). INTERVENTIONS AND METHODS: Each volunteer was administered 500 ml of 10% HES 200/0.5 in a 0.9% NaCl solution intravenously within 1 h. A gut lavage with 6 l of a polysaccharide free solution was continuously administered from 3 h prior to until 2 h after the HES infusion to facilitate the collection of the samples and to exclude any source of error at analysis. HES was quantified with the hexokinase method. MEASUREMENTS AND RESULTS: Right from the beginning of the infusion until 10 h after its completion, the cumulative HES excretion with feces (principle parameter) and urine as well as selective plasma volume and HES plasma level were measured. Six and 14 h after the infusion had been completed, the recovery rates of HES in urine were about 30% and 40%, respectively, and in plasma about 23% and 8%, respectively. By contrast, not more than a kind of "background noise amount" of HES (about 0.2 %) could be recovered in feces ( mean value in % of the infused amount of the substance). Six and 14 h after the infusion had been completed, the total recovery rates of HES were 53% and 49%, respectively. CONCLUSION: In a physiologically unimpaired gut HES 200/0.5 is not, or only to an infinitesimal extent, eliminated via the intestine. The question if there is any alternative path to renal excretion for HES still remains to be answered. As the calculated reappearance/recovery rate of HES is only about 50 % of the administered dose, further investigations as to the final fate of HES appear necessary.\n\nKröll, Wolfgang\n\n\n"
},
{
"text": "\n137954\nSelection of entropy-measure parameters for knowledge discovery in heart rate variability data.\n\nMayer, CC\n\nBachler, M\n\nHörtenhuber, M\n\nStocker, C\n\nHolzinger, A\n\nWassertheurer, S\n\nBeiträge in Fachzeitschriften\nISI:000337465100003\n25078574.0\n10.1186/1471-2105-15-S6-S2\nPMC4140209\nHeart rate variability is the variation of the time interval between consecutive heartbeats. Entropy is a commonly used tool to describe the regularity of data sets. Entropy functions are defined using multiple parameters, the selection of which is controversial and depends on the intended purpose. This study describes the results of tests conducted to support parameter selection, towards the goal of enabling further biomarker discovery.\n This study deals with approximate, sample, fuzzy, and fuzzy measure entropies. All data were obtained from PhysioNet, a free-access, on-line archive of physiological signals, and represent various medical conditions. Five tests were defined and conducted to examine the influence of: varying the threshold value r (as multiples of the sample standard deviation σ, or the entropy-maximizing rChon), the data length N, the weighting factors n for fuzzy and fuzzy measure entropies, and the thresholds rF and rL for fuzzy measure entropy. The results were tested for normality using Lilliefors' composite goodness-of-fit test. Consequently, the p-value was calculated with either a two sample t-test or a Wilcoxon rank sum test.\n The first test shows a cross-over of entropy values with regard to a change of r. Thus, a clear statement that a higher entropy corresponds to a high irregularity is not possible, but is rather an indicator of differences in regularity. N should be at least 200 data points for r = 0.2 σ and should even exceed a length of 1000 for r = rChon. The results for the weighting parameters n for the fuzzy membership function show different behavior when coupled with different r values, therefore the weighting parameters have been chosen independently for the different threshold values. The tests concerning rF and rL showed that there is no optimal choice, but r = rF = rL is reasonable with r = rChon or r = 0.2σ.\n Some of the tests showed a dependency of the test significance on the data at hand. Nevertheless, as the medical conditions are unknown beforehand, compromises had to be made. Optimal parameter combinations are suggested for the methods considered. Yet, due to the high number of potential parameter combinations, further investigations of entropy for heart rate variability data will be necessary.\n\nHolzinger, Andreas\n\n\n"
},
{
"text": "\n161879\nSoluble Urokinase Plasminogen Activator Receptor and Outcomes in Patients with Diabetes on Hemodialysis.\n\nDrechsler, C\n\nHayek, SS\n\nWei, C\n\nSever, S\n\nGenser, B\n\nKrane, V\n\nMeinitzer, A\n\nMärz, W\n\nWanner, C\n\nReiser, J\n\nBeiträge in Fachzeitschriften\nISI:000407053500010\n28495863.0\n10.2215/CJN.10881016\nPMC5544516\nSoluble urokinase plasminogen activator receptor is a novel biomarker strongly predictive of cardiovascular outcomes implicated in the pathogenesis of kidney disease. Soluble urokinase plasminogen activator receptor levels, however, correlate with declining kidney function. It is unclear whether soluble urokinase plasminogen activator receptor levels remain associated with outcomes in patients with ESRD.\n We measured plasma soluble urokinase plasminogen activator receptor levels in 1175 patients (mean age =66±8 years old, 54% men) with type 2 diabetes mellitus on hemodialysis participating in the German Diabetes and Dialysis Study followed for a median of 4 years for outcomes including all-cause death, cardiovascular events, and infection-related mortality. Survival analysis was performed using stepwise Cox proportional hazards models adjusted for potential confounders. Also, adjustments were made for inflammatory markers (C-reactive protein and leukocyte count) and the oxidative stress marker asymmetric dimethyl arginine to investigate potential mediators of the relationship between soluble urokinase plasminogen activator receptor and outcomes.\n Median soluble urokinase plasminogen activator receptor levels were 10, 21 pg/ml (interquartile range, 9105-12, 43 pg/ml). When stratified by tertiles, patients with soluble urokinase plasminogen activator receptor >11, 33 pg/ml (third tertile) had adjusted 1.6-fold higher mortality (hazard ratio, 1.60; 95% confidence interval, 1.27 to 2.03) compared with those with low soluble urokinase plasminogen activator receptor <9599 pg/ml (first tertile). Risks of sudden death and stroke were higher (adjusted hazard ratio, 1.98; 95% confidence interval, 1.27 to 3.09 and adjusted hazard ratio, 1.74; 95% confidence interval, 1.05 to 2.90, respectively), together accounting for higher incidence of cardiovascular events (adjusted hazard ratio, 1.48; 95% confidence interval, 1.15 to 1.89). Associations with outcomes persisted after adjusting for C-reactive protein, leukocyte count, and asymmetric dimethyl arginine. Addition of soluble urokinase plasminogen activator receptor to a risk factor model modestly improved risk discrimination for all-cause death (ΔC statistic, 0.02; 95% confidence interval, 0.00 to 0.03) and cardiovascular events (ΔC statistic, 0.02; 95% confidence interval, 0.00 to 0.05).\n The association of soluble urokinase plasminogen activator receptor levels with outcomes persists in patients on hemodialysis. Additional study is warranted to characterize the underlying pathways of that association, which may yield opportunities to develop new therapeutic strategies.\n Copyright © 2017 by the American Society of Nephrology.\n\nMärz, Winfried\n\nMeinitzer, Andreas\n\n\n"
},
{
"text": "\n168877\nSafety and efficacy of immunotherapy with the recombinant B-cell epitope-based grass pollen vaccine BM32.\n\nNiederberger, V\n\nNeubauer, A\n\nGevaert, P\n\nZidarn, M\n\nWorm, M\n\nAberer, W\n\nMalling, HJ\n\nPfaar, O\n\nKlimek, L\n\nPfützner, W\n\nRing, J\n\nDarsow, U\n\nNovak, N\n\nGerth van Wijk, R\n\nEckl-Dorna, J\n\nFocke-Tejkl, M\n\nWeber, M\n\nMüller, HH\n\nKlinger, J\n\nStolz, F\n\nBreit, N\n\nHenning, R\n\nValenta, R\n\nBeiträge in Fachzeitschriften\nISI:000440664400018\n29361332.0\n10.1016/j.jaci.2017.09.052\nPMC6392176\nBM32 is a grass pollen allergy vaccine based on recombinant fusion proteins consisting of nonallergenic peptides from the IgE-binding sites of the 4 major grass pollen allergens and the hepatitis B preS protein.\n We sought to study the safety and clinical efficacy of immunotherapy (allergen immunotherapy) with BM32 in patients with grass pollen-induced rhinitis and controlled asthma.\n A double-blind, placebo-controlled, multicenter allergen immunotherapy field study was conducted for 2 grass pollen seasons. After a baseline season, subjects (n = 181) were randomized and received 3 preseasonal injections of either placebo (n = 58) or a low dose (80 μg, n = 60) or high dose (160 μg, n = 63) of BM32 in year 1, respectively, followed by a booster injection in autumn. In the second year, all actively treated subjects received 3 preseasonal injections of the BM32 low dose, and placebo-treated subjects continued with placebo. Clinical efficacy was assessed by using combined symptom medication scores, visual analog scales, Rhinoconjunctivitis Quality of Life Questionnaires, and asthma symptom scores. Adverse events were graded according to the European Academy of Allergy and Clinical Immunology. Allergen-specific antibodies were determined by using ELISA, ImmunoCAP, and ImmunoCAP ISAC.\n Although statistical significance regarding the primary end point was not reached, BM32-treated subjects, when compared with placebo-treated subjects, showed an improvement regarding symptom medication, visual analog scale, Rhinoconjunctivitis Quality of Life Questionnaire, and asthma symptom scores in both treatment years. This was accompanied by an induction of allergen-specific IgG without induction of allergen-specific IgE and a reduction in the seasonally induced increase in allergen-specific IgE levels in year 2. In the first year, more grade 2 reactions were observed in the active (n = 6) versus placebo (n = 1) groups, whereas there was almost no difference in the second year.\n Injections of BM32 induced allergen-specific IgG, improved clinical symptoms of seasonal grass pollen allergy, and were well tolerated.\n Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.\n\nAberer, Werner\n\n\n"
},
{
"text": "\n170865\nOpen reduction and internal fixation of proximal humeral fractures with use of the locking proximal humerus plate. Surgical technique.\n\nKonrad, G\n\nBayer, J\n\nHepp, P\n\nVoigt, C\n\nOestern, H\n\nKääb, M\n\nLuo, C\n\nPlecko, M\n\nWendt, K\n\nKöstler, W\n\nSüdkamp, N\n\nBeiträge in Fachzeitschriften\nISI:000275214000008\n20194347.0\n10.2106/JBJS.I.01462\nNone\nThe treatment of unstable displaced proximal humeral fractures, especially in the elderly, remains controversial. The objective of the present prospective, multicenter, observational study was to evaluate the functional outcome and the complication rate after open reduction and internal fixation of proximal humeral fractures with use of a locking proximal humeral plate.\n One hundred and eighty-seven patients (mean age, 62.9 +/- 15.7 years) with an acute proximal humeral fracture were managed with open reduction and internal fixation with a locking proximal humeral plate. At the three-month, six month, nd one-year follow-up examinations, 165 (88%), 158 (84%), and 155 (83%) of the 187 patients were assessed with regard to pain, shoulder mobility, and strength. The Constant score was determined at each interval, and the Disabilities of the Arm, Shoulder and Hand (DASH) score was determined for the injured and contralateral extremities at the time of the one-year follow-up.\n Between three months and one year, the mean range of motion and the mean Constant score for the injured shoulders improved substantially. Twelve months after surgery, the mean Constant score for the injured side was 70.6 +/- 13.7 points, corresponding to 85.1% +/- 14.0% of the score for the contralateral side. The mean DASH score at the time of the one-year follow-up was 15.2 +/- 16.8 points. Sixty-two complications were encountered in fifty-two (34%) of 155 patients at the time of the one-year follow-up. Twenty-five complications (40%) were related to incorrect surgical technique and were present at the end of the operative procedure. The most common complication, noted in twenty-one (14%) of 155 patients, was intraoperative screw perforation of the humeral head. Twenty-nine patients (19%) had an unplanned second operation within twelve months after the fracture.\n Surgical treatment of displaced proximal humeral fractures with use of the locking proximal humeral plate that was evaluated in the present study can lead to a good functional outcome provided that the correct surgical technique is used. Because many of the complications were related to incorrect surgical technique, it behooves the treating surgeon to perform the operation correctly to avoid iatrogenic errors.\n\nPlecko, Michael\n\n\n"
},
{
"text": "\n739\nDifferential regulation of mesenteric and femoral blood flow in the rat as revealed by computerized data acquisition and evaluation.\n\nHeinemann, A\n\nWachter, CH\n\nHolzer, P\n\nBeiträge in Fachzeitschriften\nISI:000075328000005\n9728324.0\n10.1046/j.1365-2680.1998.1810039.x\nNone\n1. A set-up for computerized acquisition and evaluation of haemodynamic data was constructed. Blood flow (BF) in the superior mesenteric and femoral artery of urethane-anaesthetized rats was measured with the ultrasonic transit time shift technique. The signals for arterial blood pressure and BF were fed into a personal computer via an analogue-digital converter. Mean arterial blood pressure, heart rate and vascular conductance (CV) were calculated on-line. For subsequent analysis of the data, algorithms were programmed to filter the data, and to determine average and peak values for each parameter. 2. Systemic hypertension induced by phenylephrine (3-300 nmol kg-1), angiotensin II (0.1-3.0 nmol kg-1) and arginine vasopressin (0.03-1.0 nmol kg-1) was accompanied by constriction of the mesenteric artery. In contrast, the femoral artery responded to phenylephrine with constriction, to angiotensin II with dilatation and to arginine vasopressin with dilation followed by constriction. The haemodynamic effects of endothelin-1 (0.03-3.0 nmol kg-1) were generally biphasic, the initial hypotension being associated with dilatation, and the delayed hypertension being accompanied by constriction of both the mesenteric and femoral arterial bed. 3. Terbutaline (3-1.0 nmol kg-1) and calcitonin gene-related peptide (0.03-1 nmol kg-1) caused systemic hypotension along with mesenteric and femoral vasodilatation. 4. Telmisartan (1 mg kg-1), an angiotensin AT1 receptor antagonist, dilated the mesenteric artery, but had no effect on femoral VC. In contrast, the alpha 1-adrenoceptor antagonist prazosin (0.1 mg kg-1), dilated the femoral artery without altering mesenteric VC. Similarly, the beta-adrenoceptor antagonist propranolol (1 mg kg-1) had no effect on mesenteric VC, but constricted the femoral arterial bed. 5. These data demonstrate that the haemodynamic effects of exogenously administered drugs can widely differ between the mesenteric and femoral arterial beds of urethane-anaesthetized rats. Furthermore, vascular tone of these two arterial beds in maintained by different vasoconstrictor systems. While the femoral artery is mainly under adrenergic control, the renin-angiotensin axis is predominant in the mesenteric arterial bed. In addition, this study also demonstrates that computerized analysis enables quick and accurate estimation of haemodynamic drug effects, and is superior to 'by hand' evaluation of peak changes in the functional diameter of the vascular bed under study.\n\nHeinemann, Akos\n\nHolzer, Peter\n\n\n"
},
{
"text": "\n2238\nRegenerative effect of human recombinant NGF on capsaicin-lesioned sensory neurons in the adult rat.\n\nSchicho, R\n\nSkofitsch, G\n\nDonnerer, J\n\nBeiträge in Fachzeitschriften\nISI:000077846400008\n9974123.0\n10.1016%2FS0006-8993%2898%2901094-4\nNone\nNerve growth factor (NGF) has the ability to increase the content of peptide transmitter in intact primary sensory afferents of the adult rat. We have previously shown that NGF can also induce a refill of peptide transmitters in capsaicin-depleted peptidergic nerve terminals of the rat paw skin upon intraplantar injection. The present study was aimed at investigating the neurochemical, immunohistochemical and functional recovery of peripheral and central terminals of capsaicin-lesioned afferents following administration of recombinant human NGF-beta (rhNGF-beta). The systemic capsaicin treatment in adult rats by 50 mg/kg s.c. (day 0) was followed by intraplantar rhNGF-beta injections (4 micrograms each) into one hind paw on days 1, 2, 3, 5, 6 and by the analysis on day 8. The content of the marker peptide calcitonin gene-related peptide (CGRP) showed a 100% NGF-induced recovery in the peripheral (sciatic nerve) and central axons (lumbar dorsal roots) on the side of the NGF treatment and also in the contralateral sciatic nerve and lumbar dorsal roots. In the terminals of the hind paw skin, the recovery of the CGRP content, as measured by radioimmunoassay, was 100% in the plantar and 80% in the dorsal skin ipsilaterally, and 55% in the dorsal and plantar hind paw skin contralaterally. In the lumbar dorsal spinal cord, CGRP content recovered by 85% bilaterally. The morphological appearance of the sensory nerve terminals was visualized by CGRP-immunohistochemistry. In the paw skin, the CGRP-immunoreactive (CGRP-IR) nerve endings were restricted to a fragmentary subepidermal plexus after the capsaicin treatment, whereas the subsequent NGF treatment caused a bilateral recovery of the subepidermal plexus and an intact reinnervation of the epidermis and blood vessels with free nerve terminals. The capsaicin-induced fragmentation of the CGRP terminal plexus in laminae I and II of the lumbar spinal dorsal horn was also markedly repaired on both sides by the intraplantar NGF injections. The NGF treatment caused the CGRP nerve terminals in the spinal cord to regain their ability of releasing transmitter upon capsaicin stimulation as shown in tissue slice superfusion experiments. These results show that within one week, rhNGF-beta can induce a complete reinnervation of skin and spinal cord with intact CGRP-IR nerve terminals after an acute capsaicin lesion.\n\nDonnerer, Josef\n\nSchicho, Rudolf\n\n\n"
},
{
"text": "\n6269\nPrevalent vertebral deformity predicts incident hip though not distal forearm fracture: results from the European Prospective Osteoporosis Study.\n\nIsmail, AA\n\nCockerill, W\n\nCooper, C\n\nFinn, JD\n\nAbendroth, K\n\nParisi, G\n\nBanzer, D\n\nBenevolenskaya, LI\n\nBhalla, AK\n\nArmas, JB\n\nCannata, JB\n\nDelmas, PD\n\nDequeker, J\n\nDilsen, G\n\nEastell, R\n\nErshova, O\n\nFalch, JA\n\nFelsch, B\n\nHavelka, S\n\nHoszowski, K\n\nJajic, I\n\nKragl, U\n\nJohnell, O\n\nLopez Vaz, A\n\nLorenc, R\n\nLyritis, G\n\nMarchand, F\n\nMasaryk, P\n\nMatthis, C\n\nMiazgowski, T\n\nPols, HA\n\nPoor, G\n\nRapado, A\n\nRaspe, HH\n\nReid, DM\n\nReisinger, W\n\nJanott, J\n\nScheidt-Nave, C\n\nStepan, J\n\nTodd, C\n\nWeber, K\n\nWoolf, AD\n\nAmbrecht, G\n\nGowin, W\n\nFelsenberg, D\n\nLunt, M\n\nKanis, JA\n\nReeve, J\n\nSilman, AJ\n\nO'Neill, TW\n\nBeiträge in Fachzeitschriften\nISI:000167809200001\n11303719.0\n10.1007%2Fs001980170138\nNone\nThe presence of a vertebral deformity increases the risk of subsequent spinal deformities. The aim of this analysis was to determine whether the presence of vertebral deformity predicts incident hip and other limb fractures. Six thousand three hundred and forty-four men and 6788 women aged 50 years and over were recruited from population registers in 31 European centers and followed prospectively for a median of 3 years. All subjects had radiographs performed at baseline and the presence of vertebral deformity was assessed using established morphometric methods. Incident limb fractures which occurred during the follow- up period were ascertained by annual postal questionnaire and confirmed by radiographs, review of medical records and personal interview. During a total of 40348 person-years of follow-up, 138 men and 391 women sustained a limb fracture. Amongst the women, after adjustment for age, prevalent vertebral deformity was a strong predictor of incident hip fracture, (rate ratio (RR) = 4.5; 95% CI 2.1-9.4) and a weak predictor of 'other' limb fractures (RR = 1.6; 95% CI 1.1-2.4), though not distal forearm fracture (RR = 1.0; 95% CI 0.6-1.6). The predictive risk increased with increasing number of prevalent deformities, particularly for subsequent hip fracture: for two or more deformities, RR = 7.2 (95% CI 3.0-17.3). Amongst men, vertebral deformity was not associated with an increased risk of incident limb fracture though there was a nonsignificant trend toward an increased risk of hip fracture with increasing number of deformities. In summary, prevalent radiographic vertebral deformities in women are a strong predictor of hip fracture, and to a lesser extent humerus and 'other' limb fractures; however, they do not predict distal forearm fractures.\n\nWeber, Kurt\n\n\n"
},
{
"text": "\n89497\nBivalirudin and clopidogrel with and without eptifibatide for elective stenting: effects on platelet function, thrombelastographic indexes, and their relation to periprocedural infarction results of the CLEAR PLATELETS-2 (Clopidogrel with Eptifibatide to Arrest the Reactivity of Platelets) study.\n\nGurbel, PA\n\nBliden, KP\n\nSaucedo, JF\n\nSuarez, TA\n\nDiChiara, J\n\nAntonino, MJ\n\nMahla, E\n\nSingla, A\n\nHerzog, WR\n\nBassi, AK\n\nHennebry, TA\n\nGesheff, TB\n\nTantry, US\n\nBeiträge in Fachzeitschriften\nISI:000263666800002\n19232896.0\n10.1016/j.jacc.2008.10.045\nNone\nOBJECTIVES: The primary objective of this study was to compare the effect of therapy with bivalirudin alone versus bivalirudin plus eptifibatide on platelet reactivity measured by turbidometric aggregometry and thrombin-induced platelet-fibrin clot strength (TIP-FCS) measured by thrombelastography in percutaneous coronary intervention (PCI) patients. The secondary aim was to study the relation of platelet aggregation and TIP-FCS to the occurrence of periprocedural infarction. BACKGROUND: Bivalirudin is commonly administered alone to clopidogrel naïve (CN) patients and to patients on maintenance clopidogrel therapy (MT) undergoing elective stenting. The effect of adding eptifibatide to bivalirudin on platelet reactivity (PR) and TIP-FCS, and their relation to periprocedural infarction in these patients are unknown. METHODS: Patients (n = 200) stratified to clopidogrel treatment status were randomly treated with bivalirudin (n = 102) or bivalirudin plus eptifibatide (n = 98). One hundred twenty-eight CN patients were loaded with 600 mg clopidogrel immediately after stenting, and 72 MT patients were not loaded. The PR, TIP-FCS, and myonecrosis markers were serially determined. RESULTS: In CN and MT patients, bivalirudin plus eptifibatide was associated with markedly lower PR at all times (5- and 20-microM adenosine diphosphate-induced, and 15- and 25-microM thrombin receptor activator peptide-induced aggregation; p < 0.001 for all) and reduced mean TIP-FCS (p < 0.05). Patients who had a periprocedural infarction had higher mean 18-h PR (p < 0.0001) and TIP-FCS (p = 0.002). CONCLUSIONS: For elective stenting, the addition of eptifibatide to bivalirudin lowered PR to multiple agonists and the tensile strength of the TIP-FCS, 2 measurements strongly associated with periprocedural myonecrosis. Future studies of PR and TIP-FCS for elective stenting may facilitate personalized antiplatelet therapy and enhance the selection of patients for glycoprotein IIb/IIIa blockade. (Peri-Procedural Myocardial Infarction, Platelet Reactivity, Thrombin Generation, and Clot Strength: Differential Effects of Eptifibatide + Bivalirudin Versus Bivalirudin [CLEAR PLATELETS-2]; NCT00370045.\n\nMahla, Elisabeth\n\n\n"
},
{
"text": "\n99180\nThe effect of terbutaline on the absorption of pulmonary administered insulin in subjects with asthma\n\nPetersen, AH\n\nKorsatko, S\n\nKohler, G\n\nWutte, A\n\nOlschewski, H\n\nSparre, T\n\nRastam, J\n\nWollmer, P\n\nPieber, TR\n\nBeiträge in Fachzeitschriften\nISI:000274438500008\nNone\n10.1111/j.1365-2125.2009.03573.x\nNone\ncenter dot People with mild and moderate asthma have been shown to absorb less inhaled insulin than healthy subjects. center dot In people with moderate asthma, the administration of a bronchodilator before inhalation of insulin has been shown to lead to increased uptake of inhaled insulin compared with no prior administration of bronchodilator. WHAT THIS STUDY ADDS center dot This study is the first to show that in people with asthma, reduction of bronchoconstriction leads to increased absorption of inhaled insulin. center dot This study illustrates that due to the effect of terbutaline on glucose metabolism, the effect of insulin on plasma glucose is complex when terbutaline is administered concomitantly. AIM To investigate the effect of prior administration of a bronchodilator on the absorption of inhaled insulin in people with asthma treated with inhaled corticosteroids. METHODS A single-centre, randomized, open-label, two-period cross-over trial was carried out in 41 nondiabetic subjects with asthma treated with inhaled steroids, with reversible bronchoconstriction (Rev+; n = 25) or without reversible bronchoconstriction (Rev-; n = 16). A dose of 0.10 U kg-1 inhaled human insulin was administered on each dosing day with or without prior administration of the bronchodilator terbutaline (in random order). RESULTS Prior administration of terbutaline led to a 44% increase in absorption of insulin over 6 h for the Rev+ group compared with no prior administration of bronchodilator [ratio (95% confidence interval) 1.44 (1.13, 1.82), P = 0.004], whereas no effect was seen for the Rev- or the whole group. The maximum insulin concentration (C-max) increased by 34% for the Rev+ group (P = 0.018) and 17% for the whole group (P = 0.046), whereas no significant effect of prior terbutaline administration was seen for Rev-. The time to C-max was not significantly different for the Rev+ group, whereas it was approximately 30% longer after bronchodilator administration for the Rev- group (P = 0.044) and the whole group (P = 0.032). CONCLUSIONS In people with asthma and reversible bronchoconstriction, the administration of a bronchodilator prior to administration of inhaled insulin led to increased absorption of insulin, whereas no effect on insulin absorption in subjects without significant reversibility could be detected.\n\nKöhler, Gerd\n\nKorsatko, Stefan\n\nOlschewski, Horst\n\nPieber, Thomas\n\n\n"
},
{
"text": "\n137459\nNeuroinflammation and related neuropathologies in APPSL mice: further value of this in vivo model of Alzheimer's disease.\n\nLöffler, T\n\nFlunkert, S\n\nHavas, D\n\nSchweinzer, C\n\nUger, M\n\nWindisch, M\n\nSteyrer, E\n\nHutter-Paier, B\n\nBeiträge in Fachzeitschriften\nISI:000335794600002\n24886182.0\n10.1186/1742-2094-11-84\nPMC4108132\nBeyond cognitive decline, Alzheimer's disease (AD) is characterized by numerous neuropathological changes in the brain. Although animal models generally do not fully reflect the broad spectrum of disease-specific alterations, the APPSL mouse model is well known to display early plaque formation and to exhibit spatial learning and memory deficits. However, important neuropathological features, such as neuroinflammation and lipid peroxidation, and their progression over age, have not yet been described in this AD mouse model.\n Hippocampal and neocortical tissues of APPSL mice at different ages were evaluated. One hemisphere from each mouse was examined for micro- and astrogliosis as well as concomitant plaque load. The other hemisphere was evaluated for lipid peroxidation (quantified by a thiobarbituric acid reactive substances (TBARS) assay), changes in Aβ abundance (Aβ38, Aβ40 and Aβ42 analyses), as well as determination of aggregated Aβ content (Amorfix A4 assay). Finally, correlation analyses were performed to illustrate the time-dependent correlation between neuroinflammation and Aβ load (soluble, insoluble, fibrils), or lipid peroxidation, respectively.\n As is consistent with previous findings, neuroinflammation starts early and shows strong progression over age in the APPSL mouse model. An analyses of concomitant Aβ load and plaque deposition revealed a similar progression, and high correlations between neuroinflammation markers and soluble or insoluble Aβ or fibrillar amyloid plaque loads were observed. Lipid peroxidation, as measured by TBARS levels, correlates well with neuroinflammation in the neocortex but not the hippocampus. The hippocampal lipid peroxidation correlated strongly with the increase of LOC positive fiber load, whereas neocortical TBARS levels were unrelated to amyloidosis.\n These data illustrate for the first time the progression of major AD related neuropathological features other than plaque load in the APPSL mouse model. Specifically, we demonstrate that microgliosis and astrocytosis are prominent aspects of this AD mouse model. The strong correlation of neuroinflammation with amyloid burden and lipid peroxidation underlines the importance of these pathological factors for the development of AD. The new finding of a different relation of lipid peroxidation in the hippocampus and neocortical regions show that the model might contribute to the understanding of complex pathological mechanisms and their interplay in AD.\n\nSteyrer, Ernst\n\n\n"
},
{
"text": "\n151433\nQuantitative MR imaging in fracture dating--Initial results.\n\nBaron, K\n\nNeumayer, B\n\nWidek, T\n\nSchick, F\n\nScheicher, S\n\nHassler, E\n\nScheurer, E\n\nBeiträge in Fachzeitschriften\nISI:000372907900014\n26890805.0\n10.1016/j.forsciint.2016.01.020\nNone\nFor exact age determinations of bone fractures in a forensic context (e.g. in cases of child abuse) improved knowledge of the time course of the healing process and use of non-invasive modern imaging technology is of high importance. To date, fracture dating is based on radiographic methods by determining the callus status and thereby relying on an expert's experience. As a novel approach, this study aims to investigate the applicability of magnetic resonance imaging (MRI) for bone fracture dating by systematically investigating time-resolved changes in quantitative MR characteristics after a fracture event. Prior to investigating fracture healing in children, adults were examined for this study in order to test the methodology for this application. Altogether, 31 MR examinations in 17 subjects (♀: 11 ♂: 6; median age 34 ± 15 y, scanned 1-5 times over a period of up to 200 days after the fracture event) were performed on a clinical 3T MR scanner (TimTrio, Siemens AG, Germany). All subjects were treated conservatively for a fracture in either a long bone or in the collar bone. Both, qualitative and quantitative MR measurements were performed in all subjects. MR sequences for a quantitative measurement of relaxation times T1 and T2 in the fracture gap and musculature were applied. Maps of quantitative MR parameters T1, T2, and magnetisation transfer ratio (MTR) were calculated and evaluated by investigating changes over time in the fractured area by defined ROIs. Additionally, muscle areas were examined as reference regions to validate this approach. Quantitative evaluation of 23 MR data sets (12 test subjects, ♀: 7 ♂: 5) showed an initial peak in T1 values in the fractured area (T1=1895 ± 607 ms), which decreased over time to a value of 1094 ± 182 ms (200 days after the fracture event). T2 values also peaked for early-stage fractures (T2=115 ± 80 ms) and decreased to 73 ± 33 ms within 21 days after the fracture event. After that time point, no significant changes could be detected for T2. MTR remained constant at 35.5 ± 8.0% over time. The study shows that the quantitative assessment of T1 and T2 behaviour over time in the fractured region enable the generation of a novel model allowing for an objective age determination of a fracture.\n Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.\n\nHassler, Eva Maria\n\nWidek, Thomas\n\n\n"
},
{
"text": "\n161134\nTremor stability index: a new tool for differential diagnosis in tremor syndromes.\n\ndi Biase, L\n\nBrittain, JS\n\nShah, SA\n\nPedrosa, DJ\n\nCagnan, H\n\nMathy, A\n\nChen, CC\n\nMartín-Rodríguez, JF\n\nMir, P\n\nTimmerman, L\n\nSchwingenschuh, P\n\nBhatia, K\n\nDi Lazzaro, V\n\nBrown, P\n\nBeiträge in Fachzeitschriften\nISI:000404124600024\n28459950.0\n10.1093/brain/awx104\nPMC5493195\nSee Vidailhet et al. (doi:10.1093/brain/awx140) for a scientific commentary on this article.Misdiagnosis among tremor syndromes is common, and can impact on both clinical care and research. To date no validated neurophysiological technique is available that has proven to have good classification performance, and the diagnostic gold standard is the clinical evaluation made by a movement disorders expert. We present a robust new neurophysiological measure, the tremor stability index, which can discriminate Parkinson's disease tremor and essential tremor with high diagnostic accuracy. The tremor stability index is derived from kinematic measurements of tremulous activity. It was assessed in a test cohort comprising 16 rest tremor recordings in tremor-dominant Parkinson's disease and 20 postural tremor recordings in essential tremor, and validated on a second, independent cohort comprising a further 55 tremulous Parkinson's disease and essential tremor recordings. Clinical diagnosis was used as gold standard. One hundred seconds of tremor recording were selected for analysis in each patient. The classification accuracy of the new index was assessed by binary logistic regression and by receiver operating characteristic analysis. The diagnostic performance was examined by calculating the sensitivity, specificity, accuracy, likelihood ratio positive, likelihood ratio negative, area under the receiver operating characteristic curve, and by cross-validation. Tremor stability index with a cut-off of 1.05 gave good classification performance for Parkinson's disease tremor and essential tremor, in both test and validation datasets. Tremor stability index maximum sensitivity, specificity and accuracy were 95%, 95% and 92%, respectively. Receiver operating characteristic analysis showed an area under the curve of 0.916 (95% confidence interval 0.797-1.000) for the test dataset and a value of 0.855 (95% confidence interval 0.754-0.957) for the validation dataset. Classification accuracy proved independent of recording device and posture. The tremor stability index can aid in the differential diagnosis of the two most common tremor types. It has a high diagnostic accuracy, can be derived from short, cheap, widely available and non-invasive tremor recordings, and is independent of operator or postural context in its interpretation.\n © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.\n\nSchwingenschuh, Petra\n\n\n"
},
{
"text": "\n177395\nComparative study of obstetric antiphospholipid syndrome (OAPS) and non-criteria obstetric APS (NC-OAPS): report of 1640 cases from the EUROAPS registry.\n\nAlijotas-Reig, J\n\nEsteve-Valverde, E\n\nFerrer-Oliveras, R\n\nSáez-Comet, L\n\nLefkou, E\n\nMekinian, A\n\nBelizna, C\n\nRuffatti, A\n\nHoxha, A\n\nTincani, A\n\nNalli, C\n\nMarozio, L\n\nMaina, A\n\nEspinosa, G\n\nRíos-Garcés, R\n\nCervera, R\n\nCarolis, S\n\nMonteleone, G\n\nLatino, O\n\nUdry, S\n\nLLurba, E\n\nGarrido-Gimenez, C\n\nTrespidi, L\n\nGerosa, M\n\nChighizola, CB\n\nRovere-Querini, P\n\nCanti, V\n\nMayer-Pickel, K\n\nTabacco, S\n\nArnau, A\n\nTrapé, J\n\nRuiz-Hidalgo, D\n\nSos, L\n\nFarran-Codina, I\n\nEUROAPS Study Group\n\nBeiträge in Fachzeitschriften\nISI:000538792200018\n31580459.0\n10.1093/rheumatology/kez419\nNone\nTo compare clinical features, laboratory data and fetal-maternal outcomes between 1000 women with obstetric APS (OAPS) and 640 with aPL-related obstetric complications not fulfilling Sydney criteria (non-criteria OAPS, NC-OAPS).\n This was a retrospective and prospective multicentre study from the European Registry on Obstetric Antiphospholipid Syndrome.\n A total of 1650 women with 5251 episodes, 3601 of which were historical and 1650 latest episodes, were included. Altogether, 1000 cases (OAPS group) fulfilled the Sydney classification criteria and 650 (NC-OAPS group) did not. Ten NC-OAPS cases were excluded for presenting thrombosis during follow-up. All cases were classified as category I (triple positivity or double positivity for aPL) or category II (simple positivity). Overall, aPL laboratory categories showed significant differences: 29.20% in OAPS vs 17.96% in NC-OAPS (P < 0.0001) for category I, and 70.8% in OAPS vs 82% in NC-OAPS (P < 0.0001) for category II. Significant differences were observed when current obstetric complications were compared (P < 0.001). However, major differences between groups were not observed in treatment rates, livebirths and thrombotic complications. In the NC-OAPS group, 176/640 (27.5%) did not fulfil Sydney clinical criteria (subgroup A), 175/640 (27.34%) had a low titre and/or non-persistent aPL positivity but did meet the clinical criteria (subgroup B) and 289/640 (45.15%) had a high aPL titre but did not fulfil Sydney clinical criteria (subgroup C).\n Significant clinical and laboratory differences were found between groups. Fetal-maternal outcomes were similar in both groups when treated. These results suggest that we could improve our clinical practice with better understanding of NC-OAPS patients.\n © The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.\n\nMayer-Pickel, Karoline Ilse\n\n\n"
},
{
"text": "\n84752\nThird trimester fetal growth and measures of carbohydrate and lipid metabolism in umbilical venous blood at term.\n\nSpencer, JA\n\nChang, TC\n\nCrook, D\n\nProudler, A\n\nFelton, CV\n\nRobson, SC\n\nHauesler, M\n\nBeiträge in Fachzeitschriften\nISI:A1997WF39400005\n9059181.0\n10.1136/fn.76.1.F21\nPMC1720609\nAIM: To compare measures of carbohydrate and lipid metabolism in umbilical venous blood after birth at term in pregnancies with normal and retarded fetal growth during the third trimester. METHODS: Three groups of pregnancies reaching term, in which fetal growth had been prospectively monitored by repeated ultrasound measurements during the third trimester, were studied. Sequential fetal abdominal circumference measurements remained above the 10th centile in 42 (normal size, normal growth group), below the 10th centile but did not depart further than 1.5 SD (small, normal growth group), or below the 10th centile and subsequently fell away by more than 1.5 SD before delivery (small, growth retarded group). Birthweight, neonatal morphometric measures (ponderal index, mid arm:head circumference ratio, subscapular and triceps skinfold thickness), umbilical venous blood concentrations of glucose, insulin, pro-insulin, des 31, 2 proinsulin, total cholesterol, free cholesterol, cholesterol ester, triglycerides, lipoprotein (a), apolipoprotein A-1 and apolipoprotein B were measured. RESULTS: The median birthweight of the three groups was significantly different (3570, 2569, and 2277 g, respectively). Median values of ponderal index and mid arm:head circumference ratio were significantly lower in the small, growth retarded group and did not differ between the small and normal size groups with normal growth. Both groups with small fetuses had significantly lower mean glucose and cholesterol ester concentrations, and higher mean free cholesterol:cholesterol ester ratios, compared with the normal size, normal growth group. The group showing fetal growth retardation had mean total cholesterol and mean cholesterol ester concentrations that were significantly lower than those of both the other two groups. Mean des 31, 2 proinsulin concentrations were low in both groups of small fetuses, but only significantly so in the group without fetal growth retardation. Mean insulin, proinsulin, free cholesterol, triglycerides, lipoprotein(a), apolipoprotein A-1, apolipoprotein B concentrations and the ratio of A-1:B were similar in all three groups. CONCLUSION: The similarity in the umbilical venous blood carbohydrate and lipid profile at term between pregnancies with documented third trimester fetal growth retardation and those with "genetically" small babies argues against a major role for intrauterine nutritional deprivation as a cause for the association between birth-weight and subsequent adult disease.\n\n\n"
},
{
"text": "\n106173\nExternal Validation of Urinary PCA3-Based Nomograms to Individually Predict Prostate Biopsy Outcome.\n\nAuprich, M\n\nHaese, A\n\nWalz, J\n\nPummer, K\n\nde la Taille, A\n\nGraefen, M\n\nde Reijke, T\n\nFisch, M\n\nKil, P\n\nGontero, P\n\nIrani, J\n\nChun, FKH\n\nBeiträge in Fachzeitschriften\nISI:000282369800016\n20619529.0\n10.1016/j.eururo.2010.06.038\nNone\nBackground: Prior to safely adopting risk stratification tools, their performance must be tested in an external patient cohort. Objective: To assess accuracy and generalizability of previously reported, internally validated, prebiopsy prostate cancer antigen 3 (PCA3) gene-based nomograms when applied to a large, external, European cohort of men at risk of prostate cancer (PCa). Design, setting, and participants: Biopsy data, including urinary PCA3 score, were available for 621 men at risk of PCa who were participating in a European multi-institutional study. Intervention: All patients underwent a >= 10-core prostate biopsy. Biopsy indication was based on suspicious digital rectal examination, persistently elevated prostate-specific antigen level (2.5-10 ng/ml) and/or suspicious histology (atypical small acinar proliferation of the prostate, >/= two cores affected by high-grade prostatic intraepithelial neoplasia in first set of biopsies). Measurements: PCA3 scores were assessed using the Progensa assay (Gen-Probe Inc, San Diego, CA, USA). According to the previously reported nomograms, different PCA3 score codings were used. The probability of a positive biopsy was calculated using previously published logistic regression coefficients. Predicted outcomes were compared to the actual biopsy results. Accuracy was calculated using the area under the curve as a measure of discrimination; calibration was explored graphically. Results and limitations: Biopsy-confirmed PCa was detected in 255 (41.1%) men. Median PCA3 score of biopsy-negative versus biopsy-positive men was 20 versus 48 in the total cohort, 17 versus 47 at initial biopsy, and 37 versus 53 at repeat biopsy (all p <= 0.002). External validation of all four previously reported PCA3-based nomograms demonstrated equally high accuracy (0.73-0.75) and excellent calibration. The main limitations of the study reside in its early detection setting, referral scenario, and participation of only tertiary-care centers. Conclusions: In accordance with the original publication, previously developed PCA3-based nomograms achieved high accuracy and sufficient calibration. These novel nomograms represent robust tools and are thus generalizable to European men at risk of harboring PCa. Consequently, in presence of a PCA3 score, these nomograms may be safely used to assist clinicians when prostate biopsy is contemplated. (C) 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.\n\nPummer, Karl\n\n\n"
},
{
"text": "\n106909\nAntihypertensive efficacy and safety of olmesartan and ramipril in elderly patients with mild to moderate systolic and diastolic essential hypertension.\n\nMallion, JM\n\nOmboni, S\n\nBarton, J\n\nVan Mieghem, W\n\nNarkiewicz, K\n\nPanzer, PK\n\nPuig, JG\n\nStefanadis, C\n\nZweiker, R\n\nOn Behalf of the Study Group\n\nBeiträge in Fachzeitschriften\nISI:000289699700001\n21091270.0\n10.3109/08037051.2010.532332\nNone\nObjective. To compare the efficacy and safety of olmesartan medoxomil (O) and ramipril (R) in elderly patients with essential arterial hypertension. Methods. After a 2-week placebo washout, 351 elderly hypertensive patients aged 65-89 years (office sitting diastolic blood pressure, DBP, 90-109 mmHg and office sitting systolic blood pressure, SBP, 140-179 mmHg) were randomized double-blind to 12-week treatment with O 10 mg or R 2.5 mg once daily. After the first 2 and 6 weeks, doses could be doubled in non-normalized (blood pressure < 140/90 mmHg for non-diabetic and < 130/80 mmHg for diabetic) subjects, up to 40 mg for 0 and 10 mg for R. Office blood pressures were assessed at randomization, after 2, 6 and 12 weeks of treatment; 24-h ambulatory blood pressure (ABP) was recorded at randomization and after 12 weeks. Results. At week 12, in the intention-to-treat population (170 patients O and 175 R) the rate of normalized subjects was significantly larger in the O group (38.8% vs 26.3% R; p = 0.013). Baseline-adjusted mean sitting office blood pressure reduction at final visit was not significantly greater under O [SBP: 16.6 (95% confidence interval 14.0/19.2) mmHg vs 13.0 (10.4/15.6) mmHg R, p = 0.206; DBP: 11.8 (10.3/13.3) mmHg vs 10.5 (9.0/12.0) mmHg, p = 0.351]. In the subgroup of patients with valid ABP recordings (38 O and 47 R), the reduction in 24-h average blood pressure was significantly (p < 0.01) larger with O [SBP: 8.9 (9.8/8.1) and DBP: 5.7 (6.3/5.1) mmHg] than with R [6.7 (7.9/5.6) and 4.4 (5.1/3.7) mmHg]. The superiority of O was particularly evident in the last 4 h from the dosing interval. The proportion of patients with drug-related adverse events was comparable in the two groups (4.0% O vs 4.5% R), as well as the number of patients discontinuing study drug because of a side-effect (8 0 vs 7 R). Conclusions. In elderly patients with essential arterial hypertension, O provides an effective, prolonged and well tolerated blood pressure control, with significantly better blood pressure normalization than R and represents a useful option among first-line drug treatments of hypertension in this age group.\n\nZweiker, Robert\n\n\n"
},
{
"text": "\n166377\nECTRIMS/EAN guideline on the pharmacological treatment of people with multiple sclerosis.\n\nMontalban, X\n\nGold, R\n\nThompson, AJ\n\nOtero-Romero, S\n\nAmato, MP\n\nChandraratna, D\n\nClanet, M\n\nComi, G\n\nDerfuss, T\n\nFazekas, F\n\nHartung, HP\n\nHavrdova, E\n\nHemmer, B\n\nKappos, L\n\nLiblau, R\n\nLubetzki, C\n\nMarcus, E\n\nMiller, DH\n\nOlsson, T\n\nPilling, S\n\nSelmaj, K\n\nSiva, A\n\nSorensen, PS\n\nSormani, MP\n\nThalheim, C\n\nWiendl, H\n\nZipp, F\n\nBeiträge in Fachzeitschriften\nISI:000422971000015\n29352526.0\n10.1111/ene.13536\nNone\nMultiple sclerosis (MS) is a complex disease of the central nervous system. As new drugs are becoming available, knowledge on diagnosis and treatment must continuously evolve. There is therefore a need for a reference tool compiling current data on benefit and safety, to aid professionals in treatment decisions and use of resources across Europe. The European Committee of Treatment and Research in Multiple Sclerosis (ECTRIMS) and the European Academy of Neurology (EAN) have joined forces to meet this need. The objective was to develop an evidence-based clinical practice guideline for the pharmacological treatment of people with MS to guide healthcare professionals in the decision-making process.\n This guideline has been developed using the GRADE methodology and following the recently updated EAN recommendations for guideline development. Clinical questions were formulated in PICO format (patient, intervention, comparator, outcome) and outcomes were prioritized according to their relevance to clinical practice. An exhaustive literature search up to December 2016 was performed for each question and the evidence is presented narratively and, when possible, combined in a meta-analysis using a random-effects model. The quality of evidence for each outcome was rated into four categories - very high, high, low and very low - according to the risk of bias. GRADE evidence profiles were created using GRADEprofiler (GRADEpro) software (Version 3.6). The recommendations with assigned strength (strong, weak) were formulated based on the quality of evidence and the risk-benefit balance. Consensus between the panellists was reached by use of the modified nominal group technique.\n A total of 10 questions have been agreed, encompassing treatment efficacy, response criteria, strategies to address suboptimal response and safety concerns and treatment strategies in MS and pregnancy. The guideline takes into account all disease-modifying drugs approved by the European Medicine Agency at the time of publication. A total of 20 recommendations were agreed by the guideline working group members after three rounds of consensus.\n © 2018 European Academy of Neurology and European Committee of Treatment of Research in Multiple Sclerosis.\n\nFazekas, Franz\n\n\n"
},
{
"text": "\n182720\nThe Effects of Prebiotic Supplementation with OMNi-LOGiC<sup>®</sup> FIBRE on Fecal Microbiome, Fecal Volatile Organic Compounds, and Gut Permeability in Murine Neuroblastoma-Induced Tumor-Associated Cachexia.\n\nObermüller, B\n\nSinger, G\n\nKienesberger, B\n\nKlymiuk, I\n\nSperl, D\n\nStadlbauer, V\n\nHorvath, A\n\nMiekisch, W\n\nGierschner, P\n\nGrabherr, R\n\nGruber, HJ\n\nSemeraro, MD\n\nTill, H\n\nCastellani, C\n\nBeiträge in Fachzeitschriften\nISI:000557867800001\n32650568.0\n10.3390/nu12072029\nPMC7400931\nMalignant diseases can cause tumor-associated cachexia (TAC). Supplementation with prebiotic non-digestible carbohydrates exerts positive metabolic effects in experimental oncologic diseases. The aim of this project was to assess the effect of prebiotic supplementation with OMNi-LOGiC® FIBRE on intestinal microbiome, bacterial metabolism, gut permeability, and inflammation in a murine model of neuroblastoma (NB)-associated TAC. For this study, 2, 00, 00 NB cells (MHH-NB11) were implanted into athymic mice followed by daily supplementation with water or 200 mg prebiotic oligosaccharide (POS) OMNi-LOGiC® FIBRE (NB-Aqua, n = 12; NB-POS, n = 12). Three animals of each tumor group did not develop NB. The median time of tumor growth (first visibility to euthanasia) was 37 days (IQR 12.5 days) in the NB-Aqua group and 37 days (IQR 36.5 days) in the NB-POS group (p = 0.791). At euthanasia, fecal microbiome and volatile organic compounds (VOCs), gut permeability (fluorescein isothiocyanate-dextran (FITC-dextran), and gut barrier markers were measured. Values were compared to sham animals following injection of culture medium and gavage of either water or OMNi-LOGiC® FIBRE (SH-Aqua, n = 10; SH-POS, n = 10). Alpha diversity did not differ significantly between the groups. Principal coordinate analysis (PCoA) revealed clustering differences between Aqua and POS animals. Both NB and POS supplementation led to taxonomic alterations of the fecal microbiome. Of 49 VOCs, 22 showed significant differences between the groups. NB animals had significantly higher gut permeability than Aqua animals; POS did not ameliorate these changes. The pore and leak pathways of tight junctions did not differ between groups. In conclusion, our results suggest that NB-induced TAC causes increased gut permeability coupled with compositional changes in the fecal microbiome and VOC profile. Prebiotic supplementation with OMNi-LOGiC® FIBRE seemed to induce modifications of the fecal microbiome and VOC profile but did not improve gut permeability.\n\nCastellani, Christoph\n\nGruber, Hans-Jürgen\n\nHorvath, Angela\n\nKienesberger, Bernhard\n\nKlymiuk, Ingeborg\n\nObermüller, Beate\n\nSemeraro, Maria Donatella\n\nSinger, Georg\n\nSperl, Daniela Ingrid\n\nStadlbauer-Köllner, Vanessa\n\nTill, Holger\n\n\n"
}
]
}