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"text": "\n3466\nDevelopmental exposure to estrogens alters epithelial cell adhesion and gap junction proteins in the adult rat prostate.\n\nHabermann, H\n\nChang, WY\n\nBirch, L\n\nMehta, P\n\nPrins, GS\n\nBeiträge in Fachzeitschriften\nISI:000166308700041\n11145599.0\n10.1210%2Fen.142.1.359\nNone\nBrief exposure to estrogens during the neonatal period interrupts rat prostatic development by reducing branching morphogenesis and by blocking epithelial cells from entering a normal differentiation pathway. Upon aging, ventral prostates exhibit extensive hyperplasia and dysplasia suggesting that neonatal estrogens may predispose the prostate gland to preneoplastic lesions. To determine whether these prostatic lesions may be manifested through aberrant cell-to-cell communications, the present study examined specific gap junction proteins, Connexins (Cx) 32, and Cx 43, and the cell adhesion molecule, E-cadherin, in the developing, adult and aged rat prostate gland. Male rat pups were given 25 microgram estradiol benzoate or oil on days 1, 3, and 5 of life. Prostates were removed on days 1, 4, 5, 6, 10, 15, 30, or 90 or at 16 months, and frozen sections were immunostained for E-cadherin, Cx 43, and Cx 32. Colocalization studies were performed with immunofluorescence using specific antibodies for cell markers. Gap junctions in undifferentiated epithelial cells at days 1-10 of life were composed of Cx 43, which always colocalized with basal cell cytokeratins (CK 5/15). Cx 32 expression was first observed between days 10-15 and colocalized to differentiated luminal cells (CK 8/18). Cx 43 and Cx 32 never colocalized to the same cell indicating that gap junction intercellular communication differs between basal and luminal prostatic cells. While epithelial connexin expression was not initially altered in the developing prostates following estrogen exposure, adult prostates of neonatally estrogenized rats exhibited a marked decrease in Cx 32 staining and an increased proportion of Cx 43 expressing cells. In the developing prostate, E-cadherin was localized to lateral surfaces of undifferentiated epithelial cells and staining intensity increased as the cells differentiated into luminal cells. By day 30, estrogenized prostates had small foci of epithelial cells that did not immunostain for E-cadherins. In the adult and aged prostates of estrogenized rats, larger foci with differentiation defects and dysplasia were associated with a decrease or loss in E-cadherin staining. The present findings suggest that estrogen-induced changes in the expression of E-cadherin, Cx32 and Cx43 may result in impaired cell-cell adhesion and defective cell-cell communication and may be one of the key mechanisms through which changes toward a dysplastic state are mediated. These findings are significant in light of the data on human prostate cancers where carcinogenesis and progression are associated with loss of E-cadherin and a switch from Cx32 to Cx43 expression in the epithelium.\n\n\n"
},
{
"text": "\n75466\nCurrent and future strategies in interdisciplinary treatment of medulloblastomas, supratentorial PNET (primitive neuroectodermal tumors) and intracranial germ cell tumors in childhood\n\nKortmann, RD\n\nKühl, J\n\nTimmermann, B\n\nCalaminus, G\n\nDieckmann, K\n\nWurm, R\n\nSörensen, N\n\nUrban, C\n\nGöbel, U\n\nBamberg, M\n\nBeiträge in Fachzeitschriften\nISI:000171337100002\n11591018.0\n10.1007/PL00002426\nNone\nBACKGROUND: The chances for cure in medulloblastoma, supratentorial primitive neuroectodermal tumors (stPNET) and intracranial germ cell tumors have decisively improved within the last decades. Today long-term survival in the range between 60% and 80% and more than 90%, respectively, can be achieved. The low incidence of brain tumors in childhood and the necessity for optimal patient care has led to the fact that more than 90% of children are treated within national and international controlled studies today in order to assure a constant improvement of therapeutic outcome. Recent developments in neurosurgery achieved complete tumor resections in the majority of children at a low risk for morbidity and mortality. METHODS: Systemic irradiation of neuroaxis is an essential part in the management of medulloblastoma, stPNET and intracranial germ cell tumors. The introduction of quality assurance programs in radiooncology assures a precise radiotherapy of target volumes and is a prerequisite to improve survival. RESULTS: Hyperfractionated radiotherapy has the potential of increasing dose to tumor more safely without increasing the risk for late adverse effects. Pilot studies revealed excellent tumor control in medulloblastoma with acceptable acute toxicity and a long-term survival of up to 96%. In medulloblastoma stereotactic radiation techniques reveal an acceptable toxicity and promising results in tumor control in recurrent disease or as primary treatment. They are now part of future treatment protocols in case of persisting residual tumor. Radiotherapy alone in pure germinoma is continuously yielding high cure rates. In secreting germ cell tumors cisplatin containing chemotherapies in conjunction with radiotherapy achieve a long-term survival rate of 80% today. Especially in high risk medulloblastoma and secreting germ cell tumors chemotherapies are playing an increasingly important role in the interdisciplinary management. It can be expected that future developments of chemotherapeutic protocols and the introduction of new cytostatic substances will further improve the therapeutic outcome. CONCLUSIONS: The therapeutic endeavors of all those caring for children are aiming to study modifications of the therapeutic components in the interdisciplinary approach in order to optimize the therapeutic strategies. In future the affected children and young adolescents should be accrued for the forthcoming cooperative, prospective trial HIT 2000 and ongoing trial SIOP CNS GCT 96, respectively, in order to provide the body of data supporting the selection of novel and optimized approaches for future treatment strategies.\n\nUrban, Ernst-Christian\n\n\n"
},
{
"text": "\n131872\nNeuromyelitis optica in Austria in 2011: to bridge the gap between neuroepidemiological research and practice in a study population of 8.4 million people.\n\nAboul-Enein, F\n\nSeifert-Held, T\n\nMader, S\n\nKuenz, B\n\nLutterotti, A\n\nRauschka, H\n\nRommer, P\n\nLeutmezer, F\n\nVass, K\n\nFlamm-Horak, A\n\nStepansky, R\n\nLang, W\n\nFertl, E\n\nSchlager, T\n\nHeller, T\n\nEggers, C\n\nSafoschnik, G\n\nFuchs, S\n\nKraus, J\n\nAssar, H\n\nGuggenberger, S\n\nReisz, M\n\nSchnabl, P\n\nKomposch, M\n\nSimschitz, P\n\nSkrobal, A\n\nMoser, A\n\nJeschow, M\n\nStadlbauer, D\n\nFreimüller, M\n\nGuger, M\n\nSchmidegg, S\n\nFranta, C\n\nWeiser, V\n\nKoppi, S\n\nNiederkorn-Duft, M\n\nRaber, B\n\nSchmeissner, I\n\nJecel, J\n\nTinchon, A\n\nStorch, MK\n\nReindl, M\n\nBerger, T\n\nKristoferitsch, W\n\nBeiträge in Fachzeitschriften\nISI:000326597400078\n24223985.0\n10.1371/journal.pone.0079649\nPMC3818238\nIn 2008 the Austrian Task Force for Neuromyelitis Optica (NMO) started a nation-wide network for information exchange and multi-centre collaboration. Their aim was to detect all patients with NMO or NMO spectrum disorders (NMO-SD) in Austria and to analyse their disease courses and response to treatment.\n (1) As of March 2008, 1957 serum samples (of 1557 patients) have been tested with an established cell based immunofluorescence aquaporin-4 antibody (AQP4-ab) assay with a high sensitivity and specificity (both >95%). All tests were performed in a single reference laboratory (Clinical Dept. of Neurology of the Innsbruck Medical University). (2) A nation-wide survey with several calls for participation (via email newsletters, articles in the official journal of the Austrian Society of Neurology, and workshops) was initiated in 2008. All collected data will be presented in a way that allows that every individual patient can be traced back in order to ensure transparency and to avoid any data distortion in future meta-analyses. The careful and detailed presentation allows the visualization and comparison of the different disease courses in real time span. Failure and response to treatment are made visible at one glance. Database closure was 31 December 2011. All co-operators were offered co-authorship.\n All 71 NMO- or NMO-SD patients with AQP4-ab positivity (age range 12.3 to 79.6 years) were analysed in detail. Sex ratio (m:f = 1:7) and the proportion of patients without oligoclonal bands in cerebrospinal fluid (86.6%) were in line with previously published results. All identified patients were Caucasians.\n A nationwide collaboration amongst Austrian neurologists with good network communications made it possible to establish a database of 71 AQP4-ab positive patients with NMO/NMO-SD. This database is presented in detail and provides the basis for further studies and international cooperation in order to investigate this rare disease.\n\nFuchs, Siegrid\n\nSeifert-Held, Thomas\n\n\n"
},
{
"text": "\n157205\nPosterior versus Anterior Circulation Stroke in Young Adults: A Comparative Study of Stroke Aetiologies and Risk Factors in Stroke among Young Fabry Patients (sifap1).\n\nvon Sarnowski, B\n\nSchminke, U\n\nGrittner, U\n\nTanislav, C\n\nBöttcher, T\n\nHennerici, MG\n\nTatlisumak, T\n\nPutaala, J\n\nKaps, M\n\nFazekas, F\n\nEnzinger, C\n\nRolfs, A\n\nKessler, C\n\nsifap1 Investigators\n\nBeiträge in Fachzeitschriften\nISI:000399170000009\n28088807.0\n10.1159/000454840\nNone\nAlthough 20-30% of all strokes occur in the posterior circulation, few studies have explored the characteristics of patients with strokes in the posterior compared to the anterior circulation so far. Especially data on young patients is missing.\n In this secondary analysis of data of the prospective multi-centre European sifap1 study that investigated stroke and transient ischemic attack (TIA) patients aged 18-55 years, we compared vascular risk factors, stroke aetiology, presence of white matter hyperintensities (WMH) and cerebral microbleeds (CMB) between patients with ischaemic posterior circulation stroke (PCS) and those having suffered from anterior circulation stroke (ACS) based on cerebral MRI.\n We diagnosed PCS in 612 patients (29.1%, 407 men, 205 women) and ACS in 1, 89 patients (70.9%). Their age (median 46 vs. 47 years, p = 0.205) and stroke severity (modified Rankin Scale: both 2, p = 0.375, Barthel Index 90 vs. 85, p = 0.412) were similar. PCS was found to be more frequent among the male gender (66.5 vs. 60.1% with ACS, p = 0.003). Vertebral artery (VA) dissection was more often the cause of PCS (16.8%) than was carotid artery dissection of ACS (7.9%, p < 0.001). Likewise, small vessel disease (Trial of Org 10172 in Acute Stroke Treatment [TOAST] = 3, PCS: 14.7%, ACS: 11.8%) and stroke of other determined aetiology (TOAST = 4, PCS: 24.5%, ACS: 16.0%) were more frequent in those with PCS. Furthermore, patent foramen ovale (PFO; PCS: 31.1%, ACS: 25.4%, p = 0.029) was more often detected in patients with PCS. In contrast, large-artery atherosclerosis (TOAST = 1, PCS: 15.4%, ACS: 22.2%) and cardio-embolic stroke (TOAST = 2, PCS: 15.6%, ACS: 18.0%) were less frequent in those with PCS (p < 0.001) as were preceding cerebrovascular events (10.1 vs. 14.1%, p = 0.014), TIA (4.8 vs. 7.7%, p = 0.016) and smoking (53.2 vs. 61.0%, p = 0.001). The presence, extent, and location of WMH and CMB did not differ between the 2 groups.\n Our data suggested a different pattern of aetiology and risk factors in young patients with PCS compared to those with ACS. These findings especially call for a higher awareness of VA dissection and potentially for more weight of a PFO as a risk factor in young patients with PCS. Clinical trial registration-URL: http://www.clinicaltrials.gov; NCT00414583.\n © 2017 S. Karger AG, Basel.\n\nEnzinger, Christian\n\nFazekas, Franz\n\n\n"
},
{
"text": "\n184695\nWhat is Considered a Variation of Biomechanical Parameters in Tensile Tests of Collagen-Rich Human Soft Tissues? - Critical Considerations Using the Human Cranial Dura Mater as a Representative Morpho-Mechanic Model.\n\nZwirner, J\n\nScholze, M\n\nOndruschka, B\n\nHammer, N\n\nBeiträge in Fachzeitschriften\nISI:000586887900001\n33027931.0\n10.3390/medicina56100520\nPMC7600870\nBackground and Objectives: Profound knowledge on the load-dependent behavior of human soft tissues is required for the development of suitable replacements as well as for realistic computer simulations. Regarding the former, e.g., the anisotropy of a particular biological tissue has to be represented with site- and direction-dependent particular mechanical values. Contrary to this concept of consistent mechanical properties of a defined soft tissue, mechanical parameters of soft tissues scatter considerably when being determined in tensile tests. In spite of numerous measures taken to standardize the mechanical testing of soft tissues, several setup- and tissue-related factors remain to influence the mechanical parameters of human soft tissues to a yet unknown extent. It is to date unclear if measurement extremes should be considered a variation or whether these data have to be deemed incorrect measurement outliers. This given study aimed to determine mechanical parameters of the human cranial dura mater as a model for human soft tissues using a highly standardized protocol and based on this, critically evaluate the definition for the term mechanical "variation" of human soft tissue. Materials and Methods: A total of 124 human dura mater samples with an age range of 3 weeks to 94 years were uniformly retrieved, osmotically adapted and mechanically tested using customized 3D-printed equipment in a quasi-static tensile testing setup. Scanning electron microscopy of 14 samples was conducted to relate the mechanical parameters to morphological features of the dura mater. Results: The here obtained mechanical parameters were scattered (elastic modulus = 46.06 MPa, interquartile range = 33.78 MPa; ultimate tensile strength = 5.56 MPa, interquartile range = 4.09 MPa; strain at maximum force = 16.58%, interquartile range = 4.81%). Scanning electron microscopy revealed a multi-layered nature of the dura mater with varying fiber directions between its outer and inner surface. Conclusions: It is concluded that mechanical parameters of soft tissues such as human dura mater are highly variable even if a highly standardized testing setup is involved. The tissue structure and composition appeared to be the main contributor to the scatter of the mechanical parameters. In consequence, mechanical variation of soft tissues can be defined as the extremes of a biomechanical parameter due to an uncontrollable change in tissue structure and/or the respective testing setup.\n\nHammer, Niels\n\n\n"
},
{
"text": "\n186871\nFinite element based nonlinear normalization of human lumbar intervertebral disc stiffness to account for its morphology.\n\nMaquer, G\n\nLaurent, M\n\nBrandejsky, V\n\nPretterklieber, ML\n\nZysset, PK\n\nBeiträge in Fachzeitschriften\nNone\n24671515.0\n10.1115/1.4027300\nNone\nDisc degeneration, usually associated with low back pain and changes of intervertebral stiffness, represents a major health issue. As the intervertebral disc (IVD) morphology influences its stiffness, the link between mechanical properties and degenerative grade is partially lost without an efficient normalization of the stiffness with respect to the morphology. Moreover, although the behavior of soft tissues is highly nonlinear, only linear normalization protocols have been defined so far for the disc stiffness. Thus, the aim of this work is to propose a nonlinear normalization based on finite elements (FE) simulations and evaluate its impact on the stiffness of human anatomical specimens of lumbar IVD. First, a parameter study involving simulations of biomechanical tests (compression, flexion/extension, bilateral torsion and bending) on 20 FE models of IVDs with various dimensions was carried out to evaluate the effect of the disc's geometry on its compliance and establish stiffness/morphology relations necessary to the nonlinear normalization. The computed stiffness was then normalized by height (H), cross-sectional area (CSA), polar moment of inertia (J) or moments of inertia (Ixx, Iyy) to quantify the effect of both linear and nonlinear normalizations. In the second part of the study, T1-weighted MRI images were acquired to determine H, CSA, J, Ixx and Iyy of 14 human lumbar IVDs. Based on the measured morphology and pre-established relation with stiffness, linear and nonlinear normalization routines were then applied to the compliance of the specimens for each quasi-static biomechanical test. The variability of the stiffness prior to and after normalization was assessed via coefficient of variation (CV). The FE study confirmed that larger and thinner IVDs were stiffer while the normalization strongly attenuated the effect of the disc geometry on its stiffness. Yet, notwithstanding the results of the FE study, the experimental stiffness showed consistently higher CV after normalization. Assuming that geometry and material properties affect the mechanical response, they can also compensate for one another. Therefore, the larger CV after normalization can be interpreted as a strong variability of the material properties, previously hidden by the geometry's own influence. In conclusion, a new normalization protocol for the intervertebral disc stiffness in compression, flexion, extension, bilateral torsion and bending was proposed, with the possible use of MRI and FE to acquire the discs' anatomy and determine the nonlinear relations between stiffness and morphology. Such protocol may be useful to relate the disc's mechanical properties to its degree of degeneration.\n\n\n"
},
{
"text": "\n52702\nThe functional characterization of normal and neoplastic human enterochromaffin cells.\n\nModlin, IM\n\nKidd, M\n\nPfragner, R\n\nEick, GN\n\nChampaneria, MC\n\nBeiträge in Fachzeitschriften\nISI:000238095000055\n16537680.0\n10.1210/jc.2006-0110\nNone\nContext: Neuroendocrine regulation of small intestinal (SI) function is poorly understood because pure neuroendocrine cells are unavailable, whereas the biological basis of SI carcinoid tumors is unknown because neoplastic human enterochromaffin (EC) cells are unavailable. Objective: The objective of this study was to define the secretory regulation and transcriptome of naive and neoplastic SI neuroendocrine cells. Design: EC cells from human ilea were isolated and purified, and a malignant EC cell carcinoid cell line (KRJ-I) was characterized. Methods: Human ilea from right hemicolectomies were pronase/collagenase digested and Nycodenz gradient centrifuged, and EC cells were fluorescence-activated cell sorting (FACS) sorted after acridine orange labeling. Enrichment was defined by immunostaining, gene expression, serotonin (5-HT) content, and real-time RT-PCR. Naive FACS-sorted EC and KRJ-I cells were cultured, and 5-HT secretion was measured after stimulation with forskolin, isoproterenol, acetylcholine, gamma-aminobutyric acid A (GABAA), pituitary adenylate cyclase-activating polypeptide (PACAP)-38, and gastrin. Normal and neoplastic EC cell transcriptomes were acquired by Affymetrix profiling (U133A). Results: FACS produced 100 +/- 0.3% (chromogranin A staining) and 99 +/- 0.7% pure EC cells by immunostaining for tryptophan hydroxylase with greater than 67-fold enrichment and a 5-HT content of 180 +/- 18 ng/mg protein (mucosa, 3.5 +/- 0.9). Forskolin-and isoproterenol-stimulated 5-HT secretion was 10 - 100 times more potent for naive cells (EC50, 1.8 x 10(-9) M; 5.1 x 10(-9) M) than neoplastic cells (EC50, 2.1 x 10(-7) M; 8.1 x 10(-8) M), but the effect of PACAP-38 was similar (EC50, 1 x 10(-7) M). Isoproterenol stimulated cAMP levels 1.6 +/- 0.1- fold vs. basal (EC50, 2.7 x 10(-9) M). Acetylcholine inhibited naive EC cell 5-HT secretion more potently than neoplastic (IC50, 3.2 x 10(-9) vs. 1.6 x 10(-7) M), whereas GABAA was more potent in neoplastic cells (IC50, 3.9 x 10(-10) vs. 4.4 x 10(-9) M). Octreotide inhibited naive, but not neoplastic, basal 5-HT secretion. Gastrin had no effect on 5-HT secretion. Comparison of naive and neoplastic transcriptomes revealed shared neuroendocrine and EC cell-specific marker genes. Real-time PCR confirmed that expression of adrenergic (beta 1), somatostatinergic (SSTR2), and neural (VPAC1 and GABAA) receptors occurred on both cell types, but PACAP type 1 (PAC1) and cholecystokinin type 2 (CCK2) were undetectable. The putative carcinoid malignancy genes (MTA1 and MAGE-D2) were unique to the neoplastic EC cell transcriptome. Conclusion: These data support novel methodology to purify live human EC cells for functional characterization and transcriptome assessment, which will allow identification of new targets to control the secretion and proliferation of SI carcinoids.\n\n\n"
},
{
"text": "\n142473\nMatched unrelated donor marrow transplantation in patients with advanced acute leukemia.\n\nGreinix, HT\n\nReiter, E\n\nSchulenburg, A\n\nKeil, F\n\nLechner, K\n\nFischer, G\n\nRosenmayr, A\n\nLeitner, G\n\nKalhs, P\n\nBeiträge in Fachzeitschriften\nISI:000078030900017\n9916636.0\nNone\nNone\nPatients with advanced acute leukemia (AL) have a poor prognosis with death due to disease or complications of therapy. High-dose chemoradiotherapy followed by allogeneic marrow transplantation (BMT) has been used to overcome resistance of the leukemic clone resulting in long-term survival of up to 20%. Due to lack of suitable related donors BMT from an HLA-compatible unrelated donor (MUD) has been increasingly applied in these patients during the last years. Between January 1991 and August 1997 twenty five patients with advanced acute myeloid (n=19) or lymphoid (n=6) leukemia, 11 males and 14 females, age 22 to 41 (median 32) years received MUD (n=22) or 1-antigen mismatched unrelated donor (n=3) grafts. In four patients an autologous BMT had been performed previously. For conditioning all patients were given total body irradiation containing regimens. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine (CSA) and methotrexate (n=24) or CSA and methylprednisone (n=1). In 23 patients (92%) class II region compatibility was assessed by DRB1, DRB3, DRB5, and DQB1 allele typing by hybridization of amplified DNA with ligation based typing. In 2 patients HLA-DR typing was performed by two colour fluorescence cytotoxicity test and mixed lymphocyte cultures. As of November 1997 10/25 patients (40%) are surviving leukemia-free after a median observation time of 17 (range, 3 to 38) months. Transplant-related mortality was an overall of 36% and 28% in patients receiving their first BMT. In 6/25 patients (24%) relapse occurred 2 to 26 months after BMT. Incidence of acute GVHD grade I to IV was 85%. The probability of relapse projected at 3 years was 35%. High-dose chemoradiotherapy followed by MUD marrow infusion has a curative potential for patients with advanced acute leukemia and offers the chance of long-term leukemia-free survival. Currently, up to 80% of patients with acute myelogenous leukemia (AML) and acute lymphoid leukemia (ALL) under the age of 50 years achieve complete hematological remission (CR) with conventional dose chemotherapy. However, in patients who are refractory to induction chemotherapy or relapse prognosis is still poor. There, high-dose chemoradiotherapy followed by allogeneic marrow infusion has been used to overcome resistance of the refractory leukemic clone and has resulted in long-term survival. For selected patients lacking a human leukocyte antigen (HLA) compatible family donor marrow transplantation (BMT) with a suitable unrelated marrow donor (MUD) has become a feasible and effective treatment. Here, we report our experience in patients with advanced acute leukemia given marrow grafts from unrelated donors.\n\nGreinix, Hildegard\n\n\n"
},
{
"text": "\n799\nEDRF does not mediate coronary vasodilation secondary to simulated ischemia: a study on KATP channels and N omega-nitro-L-arginine on coronary perfusion pressure in isolated Langendorff-perfused guinea-pig hearts.\n\nGasser, R\n\nKöppel, H\n\nBrussee, H\n\nGrisold, M\n\nHolzmann, S\n\nKlein, W\n\nBeiträge in Fachzeitschriften\nISI:000076135500007\n9784907.0\n10.1023%2FA%3A1007717816652\nNone\nSeveral authors have alluded to the possible involvement of EDRF (NO) in ischemia-induced coronary artery dilation. Alternatively, it has been suggested that opening of ATP-dependent K channels could play a key role in this context. We studied the effects of sulfonylureas and NG-nitro-L-arginine (LNNA), a specific inhibitor of endothelial NO (EDRF) synthesis, on ischemia-induced coronary vasodilation in isolated Langendorff-perfused guinea pig hearts arrested with 15 mM KCl in normal Tyrode, and isolated pig coronary arteries precontracted with 43 mM KCl. In Isolated Langerdorff-perfused guinea pig heart, when hypoxia was simulated by switching 100% O2 in the perfusate to 100% N2, coronary perfusion pressure (CPP) fell from 90 cm H2O by 45 +/- 5 cm H2O. In the presence of LNNA, a specific inhibitor of NO synthetase in endothelial cells, CPP dropped by 44 +/- 6 cm H2O (n = 6; +/- SEM, no statistically significant). On biochemical simulation of ischemia (addition of iodoacetate [IAA]), CPP dropped 40 +/- 6 cm H2O, and in experiments performed under the same conditions but in the presence of LNNA, CPP dropped by 38 +/- 5 cm H2O (n = 6; +/- SEM; not statistically significant). When ischemia was simulated metabolically by equimolar replacement of 10 mM glucose with 2-deoxyglucose (DOG), an inhibitor of glycolysis CPP decreased by 24 +/- 1 cm H2O (n = 6; +/- SEM) after 15 minutes. This fall in CPP was almost prevented by 20 microM glibenclamide, whereas in the presence of 20 microM LNNA the DOG-induced decrease in CPP was not significantly inhibited, and CPP decreased by 22 +/- 2.6 cm H2O (n = 6; +/- SEM). In isolated pig coronary artery rings, maximal tension, achieved by depolarizing the smooth muscle cells by 43 mM KCl, decreased by 37 +/- 7% upon simulated hypoxia by replacing 100% O2 with 100% N2 in the perfusate (n = 6; +/- SEM) in arteries with intact endothelium. In arteries without endothelium, maximal tension also dropped by 35 +/- 6% (not statistically significant). In the same experiments the decrease in tension could be largely inhibited in the presence of 50 microM glibenclamide. Our results clearly show that in isolated perfused guinea pig hearts, as well as in isolated pig coronary arteries, EDRF does not play a decisive role in the coronary dilatory response to hypoxia and ischemia.\n\nBrussee, Helmut\n\nGasser, Robert\n\n\n"
},
{
"text": "\n24667\nThe cell in shock: the origin of multiple organ failure.\n\nSchlag, G\n\nRedl, H\n\nHallström, S\n\nBeiträge in Fachzeitschriften\nISI:A1991FN62300003\n1650020.0\n10.1016/0300-9572(91)90044-Y\nNone\nThe immediate organ damage seen after multiple trauma and in shock is a typical example of non-bacterial inflammation triggered by activation of various mediators of both the humoral and cellular systems. Anaphylatoxins and the low-flow syndrome during the shock phase account for increased PMN* margination, which in turn causes pulmonary leukostasis and may provoke massive mediator release by PMN (oxygen radicals, proteinases, eicosanoids, PAF etc). This probably leads to severe endothelial cell damage, especially in the lung. Adherence of PMN to the endothelium appears to create the micro-environment where high concentrations of proteolytic enzymes and reactive oxygen radicals exert a deleterious effect on the cell membrane. Endothelial cell membrane injury leads to increased vascular permeability and cell edema. The development of the 'organ in shock' may require a few hours and initially cause minor or no functional impairment at all. Only when shock is severe is there early organ failure, which in this stage may still be an expression of non-bacterial inflammation. Numerous studies have reported the existence of shock-induced cardiodepressant substances in association with various forms of circulatory shock. We have determined a net negative inotropic effect of the low-molecular-weight plasma fraction in severe hypovolemic-traumatic shock and have isolated a cardiodepressant factor (CDF), which by blockade of the calcium inward current has a negative inotropic a chronotropic effect. The intestine as a shock organ appears to range first among the organs involved. The translocation of bacteria from the intestinal tract, the 'intestine in shock' represents the trigger reaction that eventually leads from the 'organ in shock', early organ failure to late (septic) organ failure. Here the most prominent factor is endotoxin (LPS) as a basic mediator of gram-negative bacteria, which also triggers the activation of humoral and cellular systems. The posttraumatic hyperdynamic phase commonly starts on days 3-5 and is mainly caused by bacteremia and/or endotoxemia. Macrophages have a major impact on the late phase of organ failure. At present, the most prominent cellular mediator of the lethal effect of endotoxin is thought to be cachectin, which is identical with the tumor necrotising factor (TNF). TNF is secreted by monocytes/macrophages (MO/MA) in response to LPS. Via macrophage derived cytokines and by LPS there is activation of endothelial cells, with increased adhesiveness for PMN. Both due to this increased adhesiveness and the presence of LPS and cytokines, PMN undergo massive activation, which causes mediator release and tissue damage.(ABSTRACT TRUNCATED AT 400 WORDS)\n\nHallström, Seth\n\n\n"
},
{
"text": "\n65835\nDetection of complete and partial chromosome gains and losses by comparative genomic in situ hybridization.\n\ndu Manoir, S\n\nSpeicher, MR\n\nJoos, S\n\nSchröck, E\n\nPopp, S\n\nDöhner, H\n\nKovacs, G\n\nRobert-Nicoud, M\n\nLichter, P\n\nCremer, T\n\nBeiträge in Fachzeitschriften\nISI:A1993KN27800003\n8444465.0\n10.1007/BF00202476\nNone\nComparative genomic in situ hybridization (CGH) provides a new possibility for searching genomes for imbalanced genetic material. Labeled genomic test DNA, prepared from clinical or tumor specimens, is mixed with differently labeled control DNA prepared from cells with normal chromosome complements. The mixed probe is used for chromosomal in situ suppression (CISS) hybridization to normal metaphase spreads (CGH-metaphase spreads). Hybridized test and control DNA sequences are detected via different fluorochromes, e.g., fluorescein isothiocyanate (FITC) and tetraethylrhodamine isothiocyanate (TRITC). The ratios of FITC/TRITC fluorescence intensities for each chromosome or chromosome segment should then reflect its relative copy number in the test genome compared with the control genome, e.g., 0.5 for monosomies, 1 for disomies, 1.5 for trisomies, etc. Initially, model experiments were designed to test the accuracy of fluorescence ratio measurements on single chromosomes. DNAs from up to five human chromosome-specific plasmid libraries were labeled with biotin and digoxigenin in different hapten proportions. Probe mixtures were used for CISS hybridization to normal human metaphase spreads and detected with FITC and TRITC. An epifluorescence microscope equipped with a cooled charge coupled device (CCD) camera was used for image acquisition. Procedures for fluorescence ratio measurements were developed on the basis of commercial image analysis software. For hapten ratios 4/1, 1/1 and 1/4, fluorescence ratio values measured for individual chromosomes could be used as a single reliable parameter for chromosome identification. Our findings indicate (1) a tight correlation of fluorescence ratio values with hapten ratios, and (2) the potential of fluorescence ratio measurements for multiple color chromosome painting. Subsequently, genomic test DNAs, prepared from a patient with Down syndrome, from blood of a patient with T-cell prolymphocytic leukemia, and from cultured cells of a renal papillary carcinoma cell line, were applied in CGH experiments. As expected, significant differences in the fluorescence ratios could be measured for chromosome types present in different copy numbers in these test genomes, including a trisomy of chromosome 21, the smallest autosome of the human complement. In addition, chromosome material involved in partial gains and losses of the different tumors could be mapped to their normal chromosome counterparts in CGH-metaphase spreads. An alternative and simpler evaluation procedure based on visual inspection of CCD images of CGH-metaphase spreads also yielded consistent results from several independent observers. Pitfalls, methodological improvements, and potential applications of CGH analyses are discussed.\n\nSpeicher, Michael\n\n\n"
},
{
"text": "\n70949\nHow to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology.\n\nPaulus, WJ\n\nTschöpe, C\n\nSanderson, JE\n\nRusconi, C\n\nFlachskampf, FA\n\nRademakers, FE\n\nMarino, P\n\nSmiseth, OA\n\nDe Keulenaer, G\n\nLeite-Moreira, AF\n\nBorbély, A\n\nEdes, I\n\nHandoko, ML\n\nHeymans, S\n\nPezzali, N\n\nPieske, B\n\nDickstein, K\n\nFraser, AG\n\nBrutsaert, DL\n\nBeiträge in Fachzeitschriften\nISI:000250959500023\n17428822.0\n10.1093/eurheartj/ehm037\nNone\nDiastolic heart failure (DHF) currently accounts for more than 50% of all heart failure patients. DHF is also referred to as heart failure with normal left ventricular (LV) ejection fraction (HFNEF) to indicate that HFNEF could be a precursor of heart failure with reduced LVEF. Because of improved cardiac imaging and because of widespread clinical use of plasma levels of natriuretic peptides, diagnostic criteria for HFNEF needed to be updated. The diagnosis of HFNEF requires the following conditions to be satisfied: (i) signs or symptoms of heart failure; (ii) normal or mildly abnormal systolic LV function; (iii) evidence of diastolic LV dysfunction. Normal or mildly abnormal systolic LV function implies both an LVEF > 50% and an LV end-diastolic volume index (LVEDVI) <97 mL/m(2). Diagnostic evidence of diastolic LV dysfunction can be obtained invasively (LV end-diastolic pressure >16 mmHg or mean pulmonary capillary wedge pressure >12 mmHg) or non-invasively by tissue Doppler (TD) (E/E' > 15). If TD yields an E/E' ratio suggestive of diastolic LV dysfunction (15 > E/E' > 8), additional non-invasive investigations are required for diagnostic evidence of diastolic LV dysfunction. These can consist of blood flow Doppler of mitral valve or pulmonary veins, echo measures of LV mass index or left atrial volume index, electrocardiographic evidence of atrial fibrillation, or plasma levels of natriuretic peptides. If plasma levels of natriuretic peptides are elevated, diagnostic evidence of diastolic LV dysfunction also requires additional non-invasive investigations such as TD, blood flow Doppler of mitral valve or pulmonary veins, echo measures of LV mass index or left atrial volume index, or electrocardiographic evidence of atrial fibrillation. A similar strategy with focus on a high negative predictive value of successive investigations is proposed for the exclusion of HFNEF in patients with breathlessness and no signs of congestion. The updated strategies for the diagnosis and exclusion of HFNEF are useful not only for individual patient management but also for patient recruitment in future clinical trials exploring therapies for HFNEF.\n\n\n"
},
{
"text": "\n178770\nGlobal guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium.\n\nCornely, OA\n\nAlastruey-Izquierdo, A\n\nArenz, D\n\nChen, SCA\n\nDannaoui, E\n\nHochhegger, B\n\nHoenigl, M\n\nJensen, HE\n\nLagrou, K\n\nLewis, RE\n\nMellinghoff, SC\n\nMer, M\n\nPana, ZD\n\nSeidel, D\n\nSheppard, DC\n\nWahba, R\n\nAkova, M\n\nAlanio, A\n\nAl-Hatmi, AMS\n\nArikan-Akdagli, S\n\nBadali, H\n\nBen-Ami, R\n\nBonifaz, A\n\nBretagne, S\n\nCastagnola, E\n\nChayakulkeeree, M\n\nColombo, AL\n\nCorzo-León, DE\n\nDrgona, L\n\nGroll, AH\n\nGuinea, J\n\nHeussel, CP\n\nIbrahim, AS\n\nKanj, SS\n\nKlimko, N\n\nLackner, M\n\nLamoth, F\n\nLanternier, F\n\nLass-Floerl, C\n\nLee, DG\n\nLehrnbecher, T\n\nLmimouni, BE\n\nMares, M\n\nMaschmeyer, G\n\nMeis, JF\n\nMeletiadis, J\n\nMorrissey, CO\n\nNucci, M\n\nOladele, R\n\nPagano, L\n\nPasqualotto, A\n\nPatel, A\n\nRacil, Z\n\nRichardson, M\n\nRoilides, E\n\nRuhnke, M\n\nSeyedmousavi, S\n\nSidharthan, N\n\nSingh, N\n\nSinko, J\n\nSkiada, A\n\nSlavin, M\n\nSoman, R\n\nSpellberg, B\n\nSteinbach, W\n\nTan, BH\n\nUllmann, AJ\n\nVehreschild, JJ\n\nVehreschild, MJGT\n\nWalsh, TJ\n\nWhite, PL\n\nWiederhold, NP\n\nZaoutis, T\n\nChakrabarti, A\n\nMucormycosis ECMM MSG Global Guideline Writing Group\n\nBeiträge in Fachzeitschriften\nISI:000499641600003\n31699664.0\n10.1016/S1473-3099(19)30312-3\nNone\nMucormycosis is a difficult to diagnose rare disease with high morbidity and mortality. Diagnosis is often delayed, and disease tends to progress rapidly. Urgent surgical and medical intervention is lifesaving. Guidance on the complex multidisciplinary management has potential to improve prognosis, but approaches differ between health-care settings. From January, 2018, authors from 33 countries in all United Nations regions analysed the published evidence on mucormycosis management and provided consensus recommendations addressing differences between the regions of the world as part of the "One World One Guideline" initiative of the European Confederation of Medical Mycology (ECMM). Diagnostic management does not differ greatly between world regions. Upon suspicion of mucormycosis appropriate imaging is strongly recommended to document extent of disease and is followed by strongly recommended surgical intervention. First-line treatment with high-dose liposomal amphotericin B is strongly recommended, while intravenous isavuconazole and intravenous or delayed release tablet posaconazole are recommended with moderate strength. Both triazoles are strongly recommended salvage treatments. Amphotericin B deoxycholate is recommended against, because of substantial toxicity, but may be the only option in resource limited settings. Management of mucormycosis depends on recognising disease patterns and on early diagnosis. Limited availability of contemporary treatments burdens patients in low and middle income settings. Areas of uncertainty were identified and future research directions specified.\n Copyright © 2019 Elsevier Ltd. All rights reserved.\n\nHönigl, Martin\n\n\n"
},
{
"text": "\n120285\nEarly detection and intervention using neutrophil gelatinase-associated lipocalin (NGAL) may improve renal outcome of acute contrast media induced nephropathy: A randomized controlled trial in patients undergoing intra-arterial angiography (ANTI-CIN Study).\n\nSchilcher, G\n\nRibitsch, W\n\nOtto, R\n\nPortugaller, RH\n\nQuehenberger, F\n\nTruschnig-Wilders, M\n\nZweiker, R\n\nStiegler, P\n\nBrodmann, M\n\nWeinhandl, K\n\nHorina, JH\n\n\n\nBeiträge in Fachzeitschriften\nISI:000304363400001\n21849080.0\n10.1186/1471-2369-12-39\nPMC3170259\nBACKGROUND: Patients with pre-existing impaired renal function are prone to develop acute contrast media induced nephropathy (CIN). Neutrophil gelatinase-associated lipocalin (NGAL), a new biomarker predictive for acute kidney injury (AKI), has been shown to be useful for earlier diagnosis of CIN; however, urinary NGAL values may be markedly increased in chronic renal failure at baseline. Results from those studies suggested that urinary NGAL values may not be helpful for the clinician. An intravenous volume load is a widely accepted prophylactic measure and possibly a reasonable intervention to prevent deterioration of renal function. The aim of our study is to evaluate NGAL as an early predictor of CIN and to investigate the clinical benefit of early post-procedural i.v. hydration. METHODS/DESIGN: The study will follow a prospective, open-label, randomized controlled design. Patients requiring intra-arterial contrast media (CM) application will be included and receive standardized, weight-based, intravenous hydration before investigation. Subjects with markedly increased urinary NGAL values after CM application will be randomized into one of two study groups. Group A will receive 3-4 ml/kg BW/h 0.9% saline intravenously for 6 hours. Group B will undergo only standard treatment consisting of unrestricted oral fluid intake. The primary outcome measure will be CIN defined by an increase greater than 25% of baseline serum creatinine. Secondary outcomes will include urinary NGAL values, cystatin C values, contrast media associated changes in cardiac parameters such as NT-pro-BNP/troponin T, changes in urinary cytology, need for renal replacement treatment, length of stay in hospital and death.We assume that 20% of the included patients will show a definite rise in urinary NGAL. Prospective statistical power calculations indicate that the study will have 80% statistical power to detect a clinically significant decrease of CIN of 40% in the treatment arm if 1200 patients are recruited into the study. DISCUSSION: A volume expansion strategy showing a benefit from earlier intervention for patients with markedly elevated urinary NGAL values, indicating a CIN, might arise from data from this study. TRIAL REGISTRATION: ClinicalTrials.gov NCT01292317.\n\nBrodmann, Marianne\n\nHorina, Joerg\n\nPortugaller, Rupert\n\nQuehenberger, Franz\n\nRibitsch, Werner\n\nSchilcher, Gernot\n\nStiegler, Philipp\n\nZweiker, Robert\n\n\n"
},
{
"text": "\n162559\nStellarex Drug-Coated Balloon for Treatment of Femoropopliteal Disease: Twelve-Month Outcomes From the Randomized ILLUMENATE Pivotal and Pharmacokinetic Studies.\n\nKrishnan, P\n\nFaries, P\n\nNiazi, K\n\nJain, A\n\nSachar, R\n\nBachinsky, WB\n\nCardenas, J\n\nWerner, M\n\nBrodmann, M\n\nMustapha, JA\n\nMena-Hurtado, C\n\nJaff, MR\n\nHolden, AH\n\nLyden, SP\n\nBeiträge in Fachzeitschriften\nISI:000410925300004\n28729250.0\n10.1161/CIRCULATIONAHA.117.028893\nPMC5598919\nDrug-coated balloons (DCBs) are a predominant revascularization therapy for symptomatic femoropopliteal artery disease. Because of the differences in excipients, paclitaxel dose, and coating morphologies, varying clinical outcomes have been observed with different DCBs. We report the results of 2 studies investigating the pharmacokinetic and clinical outcomes of a new DCB to treat femoropopliteal disease.\n In the ILLUMENATE Pivotal Study (Prospective, Randomized, Single-Blind, U.S. Multi-Center Study to Evaluate Treatment of Obstructive Superficial Femoral Artery or Popliteal Lesions With A Novel Paclitaxel-Coated Percutaneous Angioplasty Balloon), 300 symptomatic patients (Rutherford class 2-4) were randomly assigned to DCB (n=200) or standard angioplasty (percutaneous transluminal angioplasty [PTA]) (n=100). The primary safety end point was freedom from device- and procedure-related death through 30 days, and freedom from target limb major amputation and clinically driven target lesion revascularization through 12 months. The primary effectiveness end point was primary patency through 12 months. In the ILLUMENATE PK study (Pharmacokinetic Study of the Stellarex Drug-Coated Angioplasty Balloon), paclitaxel plasma concentrations were measured after last DCB deployment and at prespecified times (at 1, 4, 24 hours and at 7 and 14 days postprocedure) until no longer detectable.\n In the ILLUMENATE Pivotal Study, baseline characteristics were similar between groups: 50% had diabetes mellitus, 41% were women, mean lesion length was 8.3 cm, and 44% were severely calcified. The primary safety end point was met (92.1% for DCB versus 83.2% for PTA, P=0.025 for superiority) and the primary patency rate was significantly higher with DCB (76.3% for DCB versus 57.6% for PTA, P=0.003). Primary patency per Kaplan-Meier estimates at day 365 was 82.3% for DCB versus 70.9% for PTA (P=0.002). The rate of clinically driven target lesion revascularization was significantly lower in the DCB cohort (7.9% versus 16.8%, P=0.023). Improvements in ankle-brachial index, Rutherford class, and quality of life were comparable, but the PTA cohort required twice as many revascularizations. Pharmacokinetic outcomes showed that all patients had detectable paclitaxel levels after DCB deployment that declined within the first hour (54.4±116.9 ng/mL to 1.4±1.0 ng/mL).\n The data demonstrate superior safety and effectiveness of the Stellarex DCB in comparison with PTA, and plasma levels of paclitaxel fall to low levels within 1 hour.\n URL: http://clinicaltrials.gov. Unique identifiers: NCT01858428 and NCT01912937.\n © 2017 The Authors.\n\nBrodmann, Marianne\n\n\n"
},
{
"text": "\n181073\nBenefit and Risks of Aspirin in Addition to Ticagrelor in Acute Coronary Syndromes: A Post Hoc Analysis of the Randomized GLOBAL LEADERS Trial.\n\nTomaniak, M\n\nChichareon, P\n\nOnuma, Y\n\nDeliargyris, EN\n\nTakahashi, K\n\nKogame, N\n\nModolo, R\n\nChang, CC\n\nRademaker-Havinga, T\n\nStorey, RF\n\nDangas, GD\n\nBhatt, DL\n\nAngiolillo, DJ\n\nHamm, C\n\nValgimigli, M\n\nWindecker, S\n\nSteg, PG\n\nVranckx, P\n\nSerruys, PW\n\nGLOBAL LEADERS Trial Investigators\n\nBeiträge in Fachzeitschriften\nISI:000501300400007\n31557763.0\n10.1001/jamacardio.2019.3355\nPMC6764000\nThe role of aspirin as part of antiplatelet regimens in acute coronary syndromes (ACS) needs to be clarified in the context of newer potent P2Y12 antagonists.\n To evaluate the benefit and risks of aspirin in addition to ticagrelor among patients with ACS beyond 1 month after percutaneous coronary intervention (PCI).\n This is a nonprespecified, post hoc analysis of GLOBAL LEADERS, a randomized, open-label superiority trial comparing 2 antiplatelet treatment strategies after PCI. The trial included 130 secondary/tertiary care hospitals in different countries, with 15 991 unselected patients with stable coronary artery disease or ACS undergoing PCI. Patients had outpatient visits at 1, 3, 6, 12, 18, and 24 months after index procedure.\n The experimental group received aspirin plus ticagrelor for 1 month followed by 23-month ticagrelor monotherapy; the reference group received aspirin plus either clopidogrel (stable coronary artery disease) or ticagrelor (ACS) for 12 months, followed by 12-month aspirin monotherapy. In this analysis, we examined the clinical outcomes occurring between 31 days and 365 days after randomization, specifically in patients with ACS who, within this time frame, were assigned to receive either ticagrelor alone or ticagrelor and aspirin.\n The primary outcome was the composite of all-cause death or new Q-wave myocardial infarction.\n Of 15 968 participants, there were 7487 patients with ACS enrolled; 3750 patients were assigned to the experimental group and 3737 patients to the reference group. Between 31 and 365 days after randomization, the primary outcome occurred in 55 patients (1.5%) in the experimental group and in 75 patients (2.0%) in the reference group (hazard ratio [HR], 0.73; 95% CI, 0.51-1.03; P = .07); investigator-reported Bleeding Academic Research Consortium-defined bleeding type 3 or 5 occurred in 28 patients (0.8%) in the experimental group and in 54 patients (1.5%) in the reference arm (HR, 0.52; 95% CI, 0.33-0.81; P = .004).\n Between 1 month and 12 months after PCI in ACS, aspirin was associated with increased bleeding risk and appeared not to add to the benefit of ticagrelor on ischemic events. These findings should be interpreted as exploratory and hypothesis generating; however, they pave the way for further trials evaluating aspirin-free antiplatelet strategies after PCI.\n ClinicalTrials.gov identifier: NCT01813435.\n\nZweiker, Robert\n\n\n"
},
{
"text": "\n182140\nGastrointestinal dysfunction in the critically ill: a systematic scoping review and research agenda proposed by the Section of Metabolism, Endocrinology and Nutrition of the European Society of Intensive Care Medicine.\n\nReintam Blaser, A\n\nPreiser, JC\n\nFruhwald, S\n\nWilmer, A\n\nWernerman, J\n\nBenstoem, C\n\nCasaer, MP\n\nStarkopf, J\n\nvan Zanten, A\n\nRooyackers, O\n\nJakob, SM\n\nLoudet, CI\n\nBear, DE\n\nElke, G\n\nKott, M\n\nLautenschläger, I\n\nSchäper, J\n\nGunst, J\n\nStoppe, C\n\nNobile, L\n\nFuhrmann, V\n\nBerger, MM\n\nOudemans-van Straaten, HM\n\nArabi, YM\n\nDeane, AM\n\nWorking Group on Gastrointestinal Function within the Section of Metabolism, Endocrinology and Nutrition (MEN Section) of ESICM\n\nBeiträge in Fachzeitschriften\nISI:000536195200002\n32414423.0\n10.1186/s13054-020-02889-4\nPMC7226709\nGastrointestinal (GI) dysfunction is frequent in the critically ill but can be overlooked as a result of the lack of standardization of the diagnostic and therapeutic approaches. We aimed to develop a research agenda for GI dysfunction for future research. We systematically reviewed the current knowledge on a broad range of subtopics from a specific viewpoint of GI dysfunction, highlighting the remaining areas of uncertainty and suggesting future studies.\n This systematic scoping review and research agenda was conducted following successive steps: (1) identify clinically important subtopics within the field of GI function which warrant further research; (2) systematically review the literature for each subtopic using PubMed, CENTRAL and Cochrane Database of Systematic Reviews; (3) summarize evidence for each subtopic; (4) identify areas of uncertainty; (5) formulate and refine study proposals that address these subtopics; and (6) prioritize study proposals via sequential voting rounds.\n Five major themes were identified: (1) monitoring, (2) associations between GI function and outcome, (3) GI function and nutrition, (4) management of GI dysfunction and (5) pathophysiological mechanisms. Searches on 17 subtopics were performed and evidence summarized. Several areas of uncertainty were identified, six of them needing consensus process. Study proposals ranked among the first ten included: prevention and management of diarrhoea; management of upper and lower feeding intolerance, including indications for post-pyloric feeding and opioid antagonists; acute gastrointestinal injury grading as a bedside tool; the role of intra-abdominal hypertension in the development and monitoring of GI dysfunction and in the development of non-occlusive mesenteric ischaemia; and the effect of proton pump inhibitors on the microbiome in critical illness.\n Current evidence on GI dysfunction is scarce, partially due to the lack of precise definitions. The use of core sets of monitoring and outcomes are required to improve the consistency of future studies. We propose several areas for consensus process and outline future study projects.\n\nAmrein, Karin\n\nFruhwald, Sonja\n\n\n"
},
{
"text": "\n3271\nThe clinical value of serum concentrations of cancer antigen 125 in patients with primary fallopian tube carcinoma: a multicenter study.\n\nHefler, LA\n\nRosen, AC\n\nGraf, AH\n\nLahousen, M\n\nKlein, M\n\nLeodolter, S\n\nReinthaller, A\n\nKainz, C\n\nTempfer, CB\n\nBeiträge in Fachzeitschriften\nISI:000089411300020\n11013371.0\n10.1002%2F1097-0142%2820001001%2989%3A7%3C1555%3A%3AAID-CNCR20%3E3.0.CO%3B2-J\nNone\nBACKGROUND: Primary fallopian tube carcinoma (PFTC) is a rare disease, and data on the serum concentration of tumor marker cancer antigen 125 (CA 125) in patients with this disease are sparse. The authors assessed the clinical value of the serum concentration of CA 125 as a prognostic and monitoring marker in patients with surgically treated PFTC. METHODS: In a multicenter study, the concentration of CA 125 was measured in 406 serum samples from 53 patients with PFTC. The results were correlated with clinical data. RESULTS: The pretreatment median serum CA 125 level was 183 U/mL (range, 6.5-5440.0 U/mL) in patients with PFTC. In a univariate Cox regression model, tumor stage and serum CA 125 level were associated significantly with shortened disease free survival (P = 0.006 and P < 0.001, respectively) and with overall survival (P = 0.03 and P = 0. 001, respectively). Lymph node involvement, tumor grade, and patient age were not associated with the length of survival. A multivariate Cox regression model showed that pretreatment the serum CA 125 level was a prognostic factor of disease free and overall survival, independent of tumor stage (P = 0.005 and P = 0.01, respectively). The pretreatment serum CA 125 level was correlated with tumor stage (P < 0.001) but not with lymph node involvement (P = 0.8), histologic grade (P = 0.3), or patient age (P = 0.2). The serum CA 125 level during chemotherapy was correlated significantly with Gynecologic Oncology Group response criteria to chemotherapy (P = 0. 001). During the follow-up of patients, serum CA 125 levels reached sensitivity, specificity, positive predictive value, and negative predictive value of 92%, 90%, 67%, and 98%, respectively, for differentiating between no evidence of disease and the presence of recurrent disease. In 90% of the patients, an increase of serum CA 125 level preceded the clinical or radiologic diagnosis of recurrent disease with a median lead time of 3 months (range, 0.5-7.0 months). CONCLUSIONS: This is the largest study to date with respect to serum CA 125 levels in patients with PFTC. The current data indicate that the pretreatment serum CA 125 level is an additional independent prognostic factor of disease free and overall survival in patients with PFTC. The serum CA 125 level adequately defines the response to chemotherapy and displays good sensitivity and specificity characteristics during the follow-up of patients with PFTC.\n\n\n"
},
{
"text": "\n80007\nSkeletal alkaline phosphatase activity is primarily released from human osteoblasts in an insoluble form, and the net release is inhibited by calcium and skeletal growth factors.\n\nAnh, DJ\n\nDimai, HP\n\nHall, SL\n\nFarley, JR\n\nBeiträge in Fachzeitschriften\nISI:000072518300011\n9504959.0\n10.1007/s002239900441\nNone\nSkeletal alkaline phosphatase (ALP) is anchored to membrane inositol-phosphate on the outer surface of osteoblasts. Although skeletal ALP activity in serum is, essentially, all in an anchorless (soluble) form, in vitro studies indicate that ALP can be released in either an anchorless, soluble form (e.g., by a phospholipase) or an anchor-intact, insoluble form (e.g., by vesicle exocytosis). The current studies were intended to define the contributions of each of these putative processes of ALP release and to assess the significance of regulation by calcium (Ca) and skeletal effectors. ALP activity was measured in serum-free medium from replicate cultures of human osteosarcoma (SaOS-2) cells and normal human bone cells. Temperature-sensitive phase distribution (in Triton X-114) allowed separation of soluble from insoluble ALP activity. Our studies revealed that most of the ALP activity released from SaOS-2 cells was in an insoluble form (78% +/- 8%), a percentage that was constant between 2 and 96 hours. A similar result was seen for normal human bone cells. Calcium had a negative, biphasic dose-dependent effect on net release of ALP activity: r = -0.85, P < 0.001 at 24 hours, with KIapparent values for biphasic inhibition of 20 and 300 mumol/l Ca. Of the skeletal effectors tested, insulin-like growth factor-II (IGF-II) had the greatest effect, decreasing the net release of ALP activity in a dose-dependent manner (r = -0.82, P < 0.005). Neither Ca nor IGF-II affected the distribution of soluble/insoluble ALP activity by more than 9%. IGF-II had no effect on extracellular ALP stability, but the addition of Ca to Ca-free cultures resulted in parallel losses of extracellular ALP activity and ALP immunoreactive protein (P < 0.001 for each). A similar effect was seen when Ca was added to Ca-free, cell-free, conditioned medium, but not when Ca was added to purified ALP, which is consistent with the general hypothesis that a Ca-dependent protease might be present in the cell-conditioned medium. Together, these data suggest that most of the ALP activity released from osteoblasts is insoluble (and, presumably, anchorless), net release of ALP activity is negatively regulated by Ca and skeletal growth factors, the effect of Ca may reflect Ca-dependent protease activity, and an exogenous (e.g., serum) phospholipase may be responsible for releasing ALP from its insoluble anchor.\n\nDimai, Hans\n\n\n"
},
{
"text": "\n156313\nZika Virus Infection in Pregnant Women in Rio de Janeiro.\n\nBrasil, P\n\nPereira, JP\n\nMoreira, ME\n\nRibeiro Nogueira, RM\n\nDamasceno, L\n\nWakimoto, M\n\nRabello, RS\n\nValderramos, SG\n\nHalai, UA\n\nSalles, TS\n\nZin, AA\n\nHorovitz, D\n\nDaltro, P\n\nBoechat, M\n\nRaja Gabaglia, C\n\nCarvalho de Sequeira, P\n\nPilotto, JH\n\nMedialdea-Carrera, R\n\nCotrim da Cunha, D\n\nAbreu de Carvalho, LM\n\nPone, M\n\nMachado Siqueira, A\n\nCalvet, GA\n\nRodrigues Baião, AE\n\nNeves, ES\n\nNassar de Carvalho, PR\n\nHasue, RH\n\nMarschik, PB\n\nEinspieler, C\n\nJanzen, C\n\nCherry, JD\n\nBispo de Filippis, AM\n\nNielsen-Saines, K\n\nBeiträge in Fachzeitschriften\nISI:000390036500004\n26943629.0\n10.1056/NEJMoa1602412\nPMC5323261\nZika virus (ZIKV) has been linked to central nervous system malformations in fetuses. To characterize the spectrum of ZIKV disease in pregnant women and infants, we followed patients in Rio de Janeiro to describe clinical manifestations in mothers and repercussions of acute ZIKV infection in infants.\n We enrolled pregnant women in whom a rash had developed within the previous 5 days and tested blood and urine specimens for ZIKV by reverse-transcriptase-polymerase-chain-reaction assays. We followed women prospectively to obtain data on pregnancy and infant outcomes.\n A total of 345 women were enrolled from September 2015 through May 2016; of these, 182 women (53%) tested positive for ZIKV in blood, urine, or both. The timing of acute ZIKV infection ranged from 6 to 39 weeks of gestation. Predominant maternal clinical features included a pruritic descending macular or maculopapular rash, arthralgias, conjunctival injection, and headache; 27% had fever (short-term and low-grade). By July 2016, a total of 134 ZIKV-affected pregnancies and 73 ZIKV-unaffected pregnancies had reached completion, with outcomes known for 125 ZIKV-affected and 61 ZIKV-unaffected pregnancies. Infection with chikungunya virus was identified in 42% of women without ZIKV infection versus 3% of women with ZIKV infection (P<0.001). Rates of fetal death were 7% in both groups; overall adverse outcomes were 46% among offspring of ZIKV-positive women versus 11.5% among offspring of ZIKV-negative women (P<0.001). Among 117 live infants born to 116 ZIKV-positive women, 42% were found to have grossly abnormal clinical or brain imaging findings or both, including 4 infants with microcephaly. Adverse outcomes were noted regardless of the trimester during which the women were infected with ZIKV (55% of pregnancies had adverse outcomes after maternal infection in the first trimester, 52% after infection in the second trimester, and 29% after infection in the third trimester).\n Despite mild clinical symptoms in the mother, ZIKV infection during pregnancy is deleterious to the fetus and is associated with fetal death, fetal growth restriction, and a spectrum of central nervous system abnormalities. (Funded by Ministério da Saúde do Brasil and others.).\n\nEinspieler, Christa\n\nMarschik, Peter\n\n\n"
}
]
}