79 results on '"Lidofsky S."'
Search Results
2. Transmembrane Electrical Potential Difference Regulates Na + /HCO - 3 Cotransport and Intracellular pH in Hepatocytes
- Author
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Fitz, J. G., Lidofsky, S. D., and Scharschmidt, B. F.
- Published
- 1992
3. Fatigue is highly associated with poor health-related quality of life, disability and depression in newly-diagnosed patients with inflammatory bowel disease, independent of disease activity
- Author
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Cohen, B. L., Zoëga, H., Shah, S. A., LeLeiko, N., Lidofsky, S., Bright, R., Flowers, N., Law, M., Moniz, H., Merrick, M., and Sands, B. E.
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- 2014
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4. Randomized placebo-controlled trial of emricasan for non-alcoholic steatohepatitis-related cirrhosis with severe portal hypertension
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Garcia-Tsao, Guadalupe, primary, Bosch, Jaime, additional, Kayali, Zeid, additional, Harrison, Stephen A., additional, Abdelmalek, Manal F., additional, Lawitz, Eric, additional, Satapathy, Sanjaya K., additional, Ghabril, Marwan, additional, Shiffman, Mitchell L., additional, Younes, Ziad H., additional, Thuluvath, Paul J., additional, Berzigotti, Annalisa, additional, Albillos, Agustin, additional, Robinson, James M., additional, Hagerty, David T., additional, Chan, Jean L., additional, Sanyal, Arun J., additional, Abdelmalek, M., additional, Bhamidimarri, K., additional, Borg, B., additional, Caldwell, S., additional, Fenkel, J., additional, Freilich, B., additional, Fuchs, M., additional, Ghabril, M., additional, Ghalib, R., additional, Gonzalez, S., additional, Gordon, S., additional, Hameed, B., additional, Harrison, S., additional, Kayali, Z., additional, Kemmer, N., additional, Korenblat, K., additional, Lai, M., additional, Landis, C., additional, Lawitz, E., additional, Lee, W., additional, Lidofsky, S., additional, Mena, E., additional, Noureddin, M., additional, Paredes, A., additional, Pyrsopoulos, N., additional, Reddy, R., additional, Rinella, M., additional, Rockey, D., additional, Rodriguez, M., additional, Ryan, M., additional, Sarkar, S., additional, Satapathy, S., additional, Scanga, A., additional, Shiffman, M., additional, Siddiqui, M., additional, Simonetto, D., additional, Syn, W., additional, Thuluvath, P., additional, Vemulapalli, R., additional, Vierling, J., additional, Younes, Z., additional, Albillos, A., additional, Ruiz-Tapiador, J. Arenas, additional, Augustin, S., additional, Calleja, J., additional, Garcia, J. Crespo, additional, Buey, L. Garcia, additional, Garcia-Pagan, J.C., additional, Villanueva, C., additional, Bureau, C., additional, Carbonell, N., additional, Leroy, V., additional, Rautou, P.-E., additional, Heinzow, H., additional, Schiefke, I., additional, Zipprich, A., additional, Berzigotti, A., additional, and Muellhaupt, B., additional
- Published
- 2020
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5. Jaundice
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LIDOFSKY, S, primary
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- 2006
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6. Impact of electronic reminder systems on hepatitis C screening in primary care
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MacLean, C. D., primary, Berger, C., additional, Cangiano, M. L., additional, Ziegelman, D., additional, and Lidofsky, S. D., additional
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- 2018
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7. Laser generation of transient photocurrents in liquids without the application of an electric field.
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Bergman, A., Dickson, C. R., Lidofsky, S. D., and Zare, R. N.
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- 1976
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8. Evaluation of Possible Inflammatory Bowel Disease: A Survey of Rhode Island Physicians
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Saha, S., Lam, M., Roberson, E., Shah, S., neal leleiko, Lidofsky, S., Bright, R., Flowers, N., Merrick, M., and Sands, B. E.
- Subjects
Adult ,Male ,Primary Health Care ,Rhode Island ,Middle Aged ,Inflammatory Bowel Diseases ,Article ,Physicians, Primary Care ,Abdominal Pain ,Health Care Surveys ,Humans ,Female ,Practice Patterns, Physicians' ,Aged - Abstract
Patients with undiagnosed inflammatory bowel disease (IBD) are often evaluated initially by primary care physicians (PCPs). Despite the frequency with which PCPs evaluate chronic abdominal pain and chronic diarrhea, little is known about how they approach these symptoms.To determine the diagnostic practices and referral patterns of PCPs when confronting a patient with potential IBD.We conducted a mail survey of PCPs practicing in Rhode Island. Clinical vignettes describing patients with chronic abdominal pain and chronic diarrhea were presented. Respondents were asked to indicate how they would evaluate these scenarios and when they would refer to a specialist.432 PCPs were surveyed; 35.6% responded. Wide variation in PCPs' definitions of chronic abdominal pain and chronic diarrhea was found, with only 26% and 51% of physicians, respectively, defining these symptoms to be chronic per standard definitions. Laboratory testing was found to vary significantly with practice type (p0.01 for 2 patient groups). Patient age influenced the ordering of diagnostic imaging (p0.0001), while patient gender did not.There is significant variability among PCPs in the threshold after which common gastrointestinal symptoms become chronic as well as in their diagnostic evaluation of these symptoms. This variability may lead to a lag in the diagnosis of IBD and influence patient outcomes.
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- 2012
9. Medical therapy of IBD in the first year after diagnosis
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Kalasapudi, B, primary, Shah, S, additional, Leleiko, N, additional, Lidofsky, S, additional, Bright, R, additional, Grabert, S, additional, Law, M, additional, Moniz, H, additional, Bancroft, B, additional, Patel, M, additional, Harris, A, additional, Cole, E, additional, Merrick, M, additional, Flowers, N, additional, and Sands, B, additional
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- 2011
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10. Ocean State Crohn's and Colitis Area Registry (OSCCAR)
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Sands, B, primary, Shah, S, additional, Leleiko, N, additional, Lidofsky, S, additional, Bright, R, additional, Grabert, S, additional, Law, M, additional, Moniz, H, additional, Bancroft, B, additional, Kalasapudi, B, additional, Cole, E, additional, Merrick, M, additional, Flowers, N, additional, Patel, M, additional, and Harris, A, additional
- Published
- 2011
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11. Presenting Symptoms at Diagnosis of Crohn's Disease and Ulcerative Colitis
- Author
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Kalasapudi, B, primary, Shah, S, additional, Leleiko, N, additional, Lidofsky, S, additional, Bright, R, additional, Grabert, S, additional, Law, M, additional, Moniz, H, additional, Bancroft, B, additional, Patel, M, additional, Harris, A, additional, Cole, E, additional, Merrick, M, additional, Flowers, N, additional, and Sands, B, additional
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- 2011
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12. Adenosine triphosphate mediates intercellular communication in liver: Talk ain't exactly cheap
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Lidofsky, S, primary
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- 1997
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13. Autocrine signaling through ATP release represents a novel mechanism for cell volume regulation.
- Author
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Wang, Y, primary, Roman, R, additional, Lidofsky, S D, additional, and Fitz, J G, additional
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- 1996
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14. Enhanced secretion of glycocholic acid in a specially adapted cell line is associated with overexpression of apparently novel ATP-binding cassette proteins.
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Brown, R S, primary, Lomri, N, additional, De Voss, J, additional, Rahmaoui, C M, additional, Xie, M H, additional, Hua, T, additional, Lidofsky, S D, additional, and Scharschmidt, B F, additional
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- 1995
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15. Cyclic AMP-dependent protein kinase activates small conductance potassium channels in liver cells
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LIDOFSKY, S, primary
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- 1993
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16. Regulation of hepatic Na(+)-HCO3- cotransport and pH by membrane potential difference
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Fitz, J. G., primary, Lidofsky, S. D., additional, and Scharschmidt, B. F., additional
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- 1993
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17. Hepatic taurocholate uptake is electrogenic and influenced by transmembrane potential difference
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Lidofsky, S. D., primary, Fitz, J. G., additional, Weisiger, R. A., additional, and Scharschmidt, B. F., additional
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- 1993
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18. Transmembrane electrical potential difference regulates Na+/HCO3- cotransport and intracellular pH in hepatocytes.
- Author
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Fitz, J. G., primary, Lidofsky, S. D., additional, Xie, M. H., additional, and Scharschmidt, B. F., additional
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- 1992
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19. Plasma membrane H(+)-HCO3- transport in rat hepatocytes: a principal role for Na(+)-coupled HCO3- transport
- Author
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Fitz, J. G., primary, Lidofsky, S. D., additional, Xie, M. H., additional, Cochran, M., additional, and Scharschmidt, B. F., additional
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- 1991
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20. Na(+)-Ca2+ exchange in cultured rat hepatocytes: evidence against a role in cytosolic Ca2+ regulation or signaling
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Lidofsky, S. D., primary, Xie, M. H., additional, and Scharschmidt, B. F., additional
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- 1990
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21. HCO3(-)-coupled Na+ influx is a major determinant of Na+ turnover and Na+/K+ pump activity in rat hepatocytes.
- Author
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Fitz, J G, Lidofsky, S D, Weisiger, R A, Xie, M H, Cochran, M, Grotmol, T, and Scharschmidt, B F
- Abstract
Recent studies in hepatocytes indicate that Na(+)-coupled HCO3- transport contributes importantly to regulation of intracellular pH and membrane HCO3- transport. However, the direction of net coupled Na+ and HCO3- movement and the effect of HCO3- on Na+ turnover and Na+/K+ pump activity are not known. In these studies, the effect of HCO3- on Na+ influx and turnover were measured in primary rat hepatocyte cultures with 22Na+, and [Na+]i was measured in single hepatocytes using the Na(+)-sensitive fluorochrome SBFI. Na+/K+ pump activity was measured in intact perfused rat liver and hepatocyte monolayers as Na(+)-dependent or ouabain-suppressible 86Rb uptake, and was measured in single hepatocytes as the effect of transient pump inhibition by removal of extracellular K+ on membrane potential difference (PD) and [Na+]i. In hepatocyte monolayers, HCO3- increased 22Na+ entry and turnover rates by 50-65%, without measurably altering 22Na+ pool size or cell volume, and HCO3- also increased Na+/K+ pump activity by 70%. In single cells, exposure to HCO3- produced an abrupt and sustained rise in [Na+]i from approximately 8 to 12 mM. Na+/K+ pump activity assessed in single cells by PD excursions during transient K+ removal increased congruent to 2.5-fold in the presence of HCO3-, and the rise in [Na+]i produced by inhibition of the Na+/K+ pump was similarly increased congruent to 2.5-fold in the presence of HCO3-. In intact perfused rat liver, HCO3- increased both Na+/K+ pump activity and O2 consumption. These findings indicate that, in hepatocytes, net coupled Na+ and HCO3- movement is inward and represents a major determinant of Na+ influx and Na+/K+ pump activity. About half of hepatic Na+/K+ pump activity appears dedicated to recycling Na+ entering in conjunction with HCO3- to maintain [Na+]i within the physiologic range. [ABSTRACT FROM AUTHOR]
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- 1991
22. Purinergic-independent calcium signaling mediates recovery from hepatocellular swelling: implications for volume regulation.
- Author
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Roe, M W, Moore, A L, and Lidofsky, S D
- Abstract
Swelling of hepatocytes and other epithelia activates volume-sensitive ion channels that facilitate fluid and electrolyte efflux to restore cell volume, but the responsible signaling pathways are incompletely defined. Previous work in model HTC rat hepatoma cells has indicated that swelling elicits ATP release, which stimulates P2 receptors and activates Cl(-) channels, and that this mechanism is essential for hepatocellular volume recovery. Since P2 receptors are generally coupled to Ca(2+) signaling pathways, we determined whether hepatocellular swelling affected cytosolic [Ca(2+)], and if this involved a purinergic mechanism. Exposure of HTC cells to hypotonic media evoked an increase in cytosolic [Ca(2+)], which was followed by activation of K(+) and Cl(-) currents. Maneuvers that interfered with swelling-induced increases in cytosolic [Ca(2+)], including extracellular Ca(2+) removal and intracellular Ca(2+) store depletion with thapsigargin, inhibited activation of membrane currents and volume recovery. However, the swelling-induced increases in cytosolic [Ca(2+)] were unaffected by either extracellular ATP depletion with apyrase or blockade of P2 receptors with suramin. These findings indicate that swelling elicits an increase in hepatocellular Ca(2+), which is essential for ion channel activation and volume recovery, but that this increase does not stem from activation of volume-sensitive P2 receptors. Collectively, these observations imply that regulatory responses to hepatocellular swelling involve a dual requirement for a purinergic-independent Ca(2+) signaling cascade and a Ca(2+)-independent purinergic signaling pathway.
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- 2001
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23. Convergent and parallel activation of low-conductance potassium channels by calcium and cAMP-dependent protein kinase.
- Author
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Lidofsky, S D
- Abstract
K+ channels, which have been linked to regulation of electrogenic solute transport as well as Ca2+ influx, represent a locus in hepatocytes for the concerted actions of hormones that employ Ca2+ and cAMP as intracellular messengers. Despite considerable study, the single-channel basis for synergistic effects of Ca2+ and cAMP on hepatocellular K+ conductance is not well understood. To address this question, patch-clamp recording techniques were applied to a model liver cell line, HTC hepatoma cells. Increasing the cytosolic Ca2+ concentration ([Ca2+]i) in HTC cells, either by activation of purinergic receptors with ATP or by inhibition of intracellular Ca2+ sequestration with thapsigargin, activated low-conductance (9-pS) K+ channels. Studies with excised membrane patches suggested that these channels were directly activated by Ca2+. Exposure of HTC cells to a permeant cAMP analog, 8-(4-chlorophenylthio)-cAMP, also activated 9-pS K+ channels but did not change [Ca2+]i. In excised membrane patches, cAMP-dependent protein kinase (the downstream effector of cAMP) activated K+ channels with conductance and selectivity identical to those of channels activated by Ca2+. In addition, cAMP-dependent protein kinase activated a distinct K+ channel type (5 pS). These data represent the differential regulation of low-conductance K+ channels by signaling pathways mediated by Ca2+ and cAMP. Moreover, since low-conductance Ca(2+)-activated K+ channels have been identified in a variety of cell types, these findings suggest that differential regulation of K+ channels by hormones with distinct signaling pathways may provide a mechanism for hormonal control of solute transport and Ca(2+)-dependent cellular functions in the liver as well as other nonexcitable tissues.
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- 1995
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24. Enzyme-linked sandwich immunoassay for insulin using laser fluorimetric detection.
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Lidofsky, S D, Hinsberg, W D, and Zare, R N
- Abstract
Human serum samples are assayed for insulin by an enzyme-linked sandwich immunoassay. Horseradish peroxidase is used as an enzyme label for antibody, and enzyme activity is measured by means of the fluorogenic substrate, p-hydroxyphenylacetic acid. The product is detected by excitation of fluorescence with the 325-nm line of a continuous-wave helium/cadmium ion laser on line with reverse-phase high-pressure liquid chromatography. The incubation period is 90 min and the limit of detection of insulin is 30 pM, corresponding to 5 microunits/ml. This method correlates highly with radioimmunoassay, with coefficient of correlation r = 0.95.
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- 1981
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25. Hepatocellular ATP-binding cassette protein expression enhances ATP release and autocrine regulation of cell volume.
- Author
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Roman, R M, Wang, Y, Lidofsky, S D, Feranchak, A P, Lomri, N, Scharschmidt, B F, and Fitz, J G
- Abstract
In a model liver cell line, recovery from swelling is mediated by a sensitive autocrine pathway involving conductive release of ATP, P2 receptor stimulation, and opening of membrane Cl- channels (Wang, Y., Roman, R. M., Lidofsky, S. D., and Fitz, J. G. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 12020-12025). However, the mechanisms coupling changes in cell volume to ATP release are not known. Based on evidence that certain ATP-binding cassette (ABC) proteins may function as ATP channels or channel regulators, we evaluated the potential role of ABC proteins by comparing ATP release and volume regulation in rat HTC and HTC-R hepatoma cells, the latter of which overexpress Mdr proteins. In both cell types, Cl- current activation (ICl-swell) and volume recovery following swelling were dependent on conductive ATP efflux. The rate of volume recovery was approximately 6-fold faster in HTC-R cells compared with HTC cells. This effect is likely due to enhanced ABC protein-dependent ATP release since (i) ICl-swell and cell volume recovery were eliminated by inhibition of P-glycoprotein transport (20 microM verapamil and 15 microM cyclosporin A); (ii) swelling-induced Cl- current density was similar in both cell types (approximately -50 pA/pF; not significant); and (iii) ATP conductance measured by whole-cell techniques was increased approximately 3-fold in HTC-R cells compared with HTC cells. Moreover, HTC-R cells exhibited enhanced survival during hypotonic stress. By modulating ATP release, hepatic ABC proteins may play a key role in the cellular pathways coupling changes in cell volume to ion permeability and secretion.
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- 1997
26. Laser fluorescence immunoassay of insulin
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Lidofsky, S. D., primary, Imasaka, T., additional, and Zare, R. N., additional
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- 1979
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27. Evaluation and management of jaundice.
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Scharschmidt, B. and Lidofsky, S.
- Abstract
Presents a diagram on the evaluation and management of jaundice.
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- 1996
28. Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial
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Zobair M Younossi, Vlad Ratziu, Rohit Loomba, Mary Rinella, Quentin M Anstee, Zachary Goodman, Pierre Bedossa, Andreas Geier, Susanne Beckebaum, Philip N Newsome, David Sheridan, Muhammad Y Sheikh, James Trotter, Whitfield Knapple, Eric Lawitz, Manal F Abdelmalek, Kris V Kowdley, Aldo J Montano-Loza, Jerome Boursier, Philippe Mathurin, Elisabetta Bugianesi, Giuseppe Mazzella, Antonio Olveira, Helena Cortez-Pinto, Isabel Graupera, David Orr, Lise Lotte Gluud, Jean-Francois Dufour, David Shapiro, Jason Campagna, Luna Zaru, Leigh MacConell, Reshma Shringarpure, Stephen Harrison, Arun J Sanyal, Manal Abdelmalek, Gary Abrams, Humberto Aguilar, Aijaz Ahmed, Elmar Aigner, Guruprasad Aithal, Aftab Ala, William Alazawi, Agustin Albillos, Michael Allison, Sfa Al-Shamma, Raul Andrade, Pietro Andreone, Mario Angelico, Victor Ankoma-Sey, Quentin Anstee, Rodolphe Anty, Victor Araya, Juan Ignacio Arenas Ruiz, Perttu Arkkila, Marty Arora, Tarik Asselah, Jennifer Au, Oyekoya Ayonrinde, Robert James Bailey, Maya Balakrishnan, Kiran Bambha, Meena Bansal, Sidney Barritt, John Bate, Jorge Beato, Jaideep Behari, Pablo Bellot, Ziv Ben Ari, Michael Bennett, Marina Berenguer, Benedetta Terziroli Beretta-Piccoli, Thomas Berg, Maurizio Bonacini, Lucia Bonet, Brian Borg, Marc Bourliere, William Bowman, David Bradley, Marija Brankovic, Marius Braun, Jean-Pierre Bronowicki, Savino Bruno, Cindy Cai, Amy Calderon, José Luis Calleja Panero, Elizabeth Carey, Michal Carmiel, Jose Antonio Carrión, Matthew Cave, Cristina Chagas, Tawfik Chami, Alan Chang, Allan Coates, Jeremy Cobbold, Charlote Costentin, Kathleen Corey, Lynsey Corless, Javier Crespo, Oscar Cruz Pereira, Victor de Ledinghen, Andrew deLemos, Moises Diago, Mamie Dong, Jean-François Dufour, Predrag Dugalic, Winston Dunn, Magby Elkhashab, Michael Epstein, Maria Desamparados Escudero-Garcia, Ohad Etzion, Larry Evans, Robert Falcone, Conrado Fernandez, Jose Ferreira, Scott Fink, Kevin Finnegan, Roberto Firpi-Morell, Annarosa Floreani, Thierry Fontanges, Ryan Ford, Ewan Forrest, Andrew Fowell, Anna Ludovica Fracanzani, Sven Francque, Bradley Freilich, Juan Frias, Michael Fuchs, Javier Fuentes, Michael Galambos, Juan Gallegos, Anja Geerts, Jacob George, Maged Ghali, Reem Ghalib, Pierre Gholam, Pere Gines, Norman Gitlin, Tobias Goeser, John Goff, Stuart Gordon, Frederic Gordon, Odile Goria, Shaun Greer, Alla Grigorian, Henning Gronbaek, Maeva Guillaume, Naresh Gunaratnam, Dina Halegoua-De Marzio, Bilal Hameed, Stephanie Hametner, James Hamilton, Marek Hartleb, Tarek Hassanein, Dieter Häussinger, Paul Hellstern, Robert Herring, Eva Heurich, Christophe Hezode, Holger Hinrichsen, Peter Holland Fischer, Yves Horsmans, Jonathan Huang, Hyder Hussaini, Antoine Jakiche, Lennox Jeffers, Blake Jones, Rosa Jorge, Francisco Jorquera, Shoba Joshi, Alisan Kahraman, Kelly Kaita, Nicholas Karyotakis, Zeid Kayali, Stergios Kechagias, Thomas Kepczyk, Mandana Khalili, Hicham Khallafi, Johannes Kluwe, Anita Kohli, Kevin Korenblat, Kris Kowdley, Aleksander Krag, Richard Krause, Andreas Kremer, Karen Krok, Miodrag Krstic, Marcelo Kugelmas, Sonal Kumar, Scott Kuwada, Damien Labarriere, Michelle Lai, Wim Laleman, Pietro Lampertico, Alice Lee, Vincent Leroy, Steven Lidofsky, Tina Huey Lim, Joseph Lim, Donald Lipkis, Ester Little, Amadeo Lonardo, Michelle Long, Velimir Anthony Christopher Luketic, Yoav Lurie, Guilherme Macedo, Joana Magalhaes, Mihály Makara, Benedict Maliakkal, Michael Manns, Pinelopi Manousou, Parvez Mantry, Giulio Marchesini, Carla Marinho, Paul Marotta, Hanns-Ulrich Marschall, Linda Martinez, Marlyn Mayo, Mark McCullen, William McLaughlin, Uta Merle, Raphael Merriman, Apurva Modi, Esther Molina, Aldo Montano-Loza, Carlos Monteverde, Amilcar Morales Cardona, Sulleman Moreea, Christophe Moreno, Filomena Morisco, Abdullah Mubarak, Beat Muellhaupt, Sandeep Mukherjee, Tobias Müller, Aleksandar Nagorni, Jahnavi Naik, Guy Neff, Moises Nevah, Philip Newsome, Eric Nguyen-Khac, Mazen Noureddin, Jude Oben, Hans Orlent, James Orr, Grisell Ortiz-Lasanta, Violaine Ozenne, Prashant Pandya, Angelo Paredes, James Park, Joykumar Patel, Keyur Patel, Sonali Paul, Heather Patton, Markus Peck-Radosavljevic, Salvatore Petta, Stephen Pianko, Anna Piekarska, Neville Pimstone, Joseph Pisegna, Paul Pockros, Stanislas Pol, Michael Porayko, John Poulos, David Pound, Joe Pouzar, Jose Presa Ramos, Nikolaos Pyrsopoulos, Nila Rafiq, Kate Muller, Alnoor Ramji, Ravi Ravinuthala, Chakradhar Reddy, Gautham Reddy K G, K. Rajender Reddy K R, Frederic Regenstein, Robert Reindollar, Justin Reynolds, Andres Riera, Jose Rivera Acosta, Geert Robaeys, Stuart Roberts, Federico Rodriguez-Perez, Sandor Romero, Manuel Romero-Gomez, Raymond Rubin, Mariagrazia Rumi, Simon Rushbrook, Christian Rust, Michael Ryan, Rifaat Safadi, Adnan Said, Kimmo Salminen, Didier Samuel, John Santoro, Arun Sanyal, Souvik Sarkar, Cynthia Schaeffer, Jörn Schattenberg, Ingolf Schiefke, Eugene Schiff, Wolfgang Schmidt, Jeffrey Schneider, Jeoffrey Schouten, Michael Schultz, Giada Sebastiani, David Semela, Thomas Sepe, Aasim Sheikh, Muhammad Sheikh, Kenneth Sherman, Oren Shibolet, Mitchell Shiffman, Asma Siddique, Cyril Sieberhagen, Samuel Sigal, Katarzyna Sikorska, Krzysztof Simon, Marie Sinclair, Richard Skoien, Joel Solis, Siddharth Sood, Bob Souder, James Spivey, Per Stal, Laura Stinton, Simone Strasser, Petar Svorcan, Gyongzi Szabo, Andrew Talal, Edward Tam, Brent Tetri, Paul Thuluvath, Hillel Tobias, Krzysztof Tomasiewicz, Dawn Torres, Albert Tran, Michael Trauner, Christian Trautwein, Emanuel Tsochatzis, Esther Unitt, Victor Vargas, Istvan Varkonyi, Ella Veitsman, Umberto Vespasiani Gentilucci, David Victor, John Vierling, Catherine Vincent, Aron Vincze, Manfred von der Ohe, Natasha Von Roenn, Raj Vuppalanchi, Michael Waters, Kymberly Watt, Julia Wattacheril, Martin Weltman, Amanda Wieland, Gregory Wiener, Alonzo Williams A, Jeffrey Williams J, Jason Wilson, Maria Yataco, Eric Yoshida, Ziad Younes, Liyun Yuan, Adam Zivony, Donald Zogg, Heinz Zoller, Fabien Zoulim, Eli Zuckerman, Massimo Zuin, Younossi Z.M., Ratziu V., Loomba R., Rinella M., Anstee Q.M., Goodman Z., Bedossa P., Geier A., Beckebaum S., Newsome P.N., Sheridan D., Sheikh M.Y., Trotter J., Knapple W., Lawitz E., Abdelmalek M.F., Kowdley K.V., Montano-Loza A.J., Boursier J., Mathurin P., Bugianesi E., Mazzella G., Olveira A., Cortez-Pinto H., Graupera I., Orr D., Gluud L.L., Dufour J.-F., Shapiro D., Campagna J., Zaru L., MacConell L., Shringarpure R., Harrison S., Sanyal A.J., Abdelmalek M., Abrams G., Aguilar H., Ahmed A., Aigner E., Aithal G., Ala A., Alazawi W., Albillos A., Allison M., Al-Shamma S., Andrade R., Andreone P., Angelico M., Ankoma-Sey V., Anstee Q., Anty R., Araya V., Arenas Ruiz J.I., Arkkila P., Arora M., Asselah T., Au J., Ayonrinde O., Bailey R.J., Balakrishnan M., Bambha K., Bansal M., Barritt S., Bate J., Beato J., Behari J., Bellot P., Ben Ari Z., Bennett M., Berenguer M., Beretta-Piccoli B.T., Berg T., Bonacini M., Bonet L., Borg B., Bourliere M., Bowman W., Bradley D., Brankovic M., Braun M., Bronowicki J.-P., Bruno S., Cai C., Calleja Panero J.L., Carey E., Carmiel M., Carrion J.A., Cave M., Chagas C., Chami T., Chang A., Coates A., Cobbold J., Corey K., Corless L., Crespo J., Cruz Pereira O., de Ledinghen V., deLemos A., Diago M., Dugalic P., Dunn W., Elkhashab M., Epstein M., Escudero-Garcia M.D., Etzion O., Evans L., Falcone R., Fernandez C., Ferreira J., Fink S., Finnegan K., Firpi-Morell R., Floreani A., Fontanges T., Ford R., Forrest E., Fowell A., Fracanzani A.L., Francque S., Freilich B., Frias J., Fuchs M., Fuentes J., Galambos M., Gallegos J., Geerts A., George J., Ghali M., Ghalib R., Gholam P., Gines P., Gitlin N., Goeser T., Goff J., Gordon S., Gordon F., Goria O., Greer S., Grigorian A., Gronbaek H., Guillaume M., Gunaratnam N., Halegoua-De Marzio D., Hameed B., Hametner S., Hamilton J., Hartleb M., Hassanein T., Haussinger D., Hellstern P., Herring R., Heurich E., Hezode C., Hinrichsen H., Holland Fischer P., Horsmans Y., Huang J., Jakiche A., Jeffers L., Jones B., Jorge R., Jorquera F., Kahraman A., Kaita K., Karyotakis N., Kayali Z., Kechagias S., Kepczyk T., Khalili M., Khallafi H., Kluwe J., Kohli A., Korenblat K., Kowdley K., Krag A., Krause R., Kremer A., Krok K., Krstic M., Kugelmas M., Kumar S., Labarriere D., Lai M., Lampertico P., Lee A., Leroy V., Lidofsky S., Lim T.H., Lim J., Lipkis D., Little E., Lonardo A., Long M., Lurie Y., Macedo G., Makara M., Maliakkal B., Manns M., Manousou P., Mantry P., Marchesini G., Marinho C., Marotta P., Marschall H.-U., Mayo M., McCullen M., McLaughlin W., Merriman R., Modi A., Molina E., Montano-Loza A., Monteverde C., Moreea S., Moreno C., Morisco F., Mubarak A., Muellhaupt B., Mukherjee S., Muller T., Nagorni A., Naik J., Neff G., Nevah M., Newsome P., Nguyen-Khac E., Noureddin M., Oben J., Orlent H., Orr J., Ortiz-Lasanta G., Ozenne V., Pandya P., Paredes A., Park J., Patel J., Patel K., Uta M., Patton H., Peck-Radosavljevic M., Petta S., Pianko S., Piekarska A., Pimstone N., Pockros P., Pol S., Porayko M., Poulos J., Pound D., Pouzar J., Presa Ramos J., Pyrsopoulos N., Rafiq N., Muller K., Ramji A., Ravinuthala R., Reddy C., Reddy K G G., Reddy K R K.R., Regenstein F., Reindollar R., Riera A., Rivera Acosta J., Robaeys G., Roberts S., Rodriguez-Perez F., Romero-Gomez M., Rubin R., Rumi M., Rushbrook S., Rust C., Ryan M., Safadi R., Said A., Salminen K., Samuel D., Santoro J., Sanyal A., Sarkar S., Schaeffer C., Schattenberg J., Schiefke I., Schiff E., Schmidt W., Schneider J., Schouten J., Schultz M., Sebastiani G., Semela D., Sepe T., Sheikh A., Sheikh M., Sherman K., Shibolet O., Shiffman M., Siddique A., Sieberhagen C., Sigal S., Sikorska K., Simon K., Sinclair M., Skoien R., Solis J., Sood S., Souder B., Spivey J., Stal P., Stinton L., Strasser S., Svorcan P., Szabo G., Talal A., Tam E., Tetri B., Thuluvath P., Tobias H., Tomasiewicz K., Torres D., Trauner M., Trautwein C., Tsochatzis E., Unitt E., Vargas V., Varkonyi I., Veitsman E., Vespasiani Gentilucci U., Victor D., Vierling J., Vincent C., Vincze A., von der Ohe M., Von Roenn N., Vuppalanchi R., Waters M., Watt K., Weltman M., Wieland A., Wiener G., Williams A A., Williams J J., Wilson J., Yataco M., Yoshida E., Younes Z., Yuan L., Zivony A., Zogg D., Zoller H., Zoulim F., Zuckerman E., Zuin M., Repositório da Universidade de Lisboa, Younossi, Z. M., Ratziu, V., Loomba, R., Rinella, M., Anstee, Q. M., Goodman, Z., Bedossa, P., Geier, A., Beckebaum, S., Newsome, P. N., Sheridan, D., Sheikh, M. Y., Trotter, J., Knapple, W., Lawitz, E., Abdelmalek, M. F., Kowdley, K. V., Montano-Loza, A. J., Boursier, J., Mathurin, P., Bugianesi, E., Mazzella, G., Olveira, A., Cortez-Pinto, H., Graupera, I., Orr, D., Gluud, L. L., Dufour, J. -F., Shapiro, D., Campagna, J., Zaru, L., Macconell, L., Shringarpure, R., Harrison, S., Sanyal, A. J., Abdelmalek, M., Abrams, G., Aguilar, H., Ahmed, A., Aigner, E., Aithal, G., Ala, A., Alazawi, W., Albillos, A., Allison, M., Al-Shamma, S., Andrade, R., Andreone, P., Angelico, M., Ankoma-Sey, V., Anstee, Q., Anty, R., Araya, V., Arenas Ruiz, J. I., Arkkila, P., Arora, M., Asselah, T., Au, J., Ayonrinde, O., Bailey, R. J., Balakrishnan, M., Bambha, K., Bansal, M., Barritt, S., Bate, J., Beato, J., Behari, J., Bellot, P., Ben Ari, Z., Bennett, M., Berenguer, M., Beretta-Piccoli, B. T., Berg, T., Bonacini, M., Bonet, L., Borg, B., Bourliere, M., Bowman, W., Bradley, D., Brankovic, M., Braun, M., Bronowicki, J. -P., Bruno, S., Cai, C., Calleja Panero, J. L., Carey, E., Carmiel, M., Carrion, J. A., Cave, M., Chagas, C., Chami, T., Chang, A., Coates, A., Cobbold, J., Corey, K., Corless, L., Crespo, J., Cruz Pereira, O., de Ledinghen, V., Delemos, A., Diago, M., Dugalic, P., Dunn, W., Elkhashab, M., Epstein, M., Escudero-Garcia, M. D., Etzion, O., Evans, L., Falcone, R., Fernandez, C., Ferreira, J., Fink, S., Finnegan, K., Firpi-Morell, R., Floreani, A., Fontanges, T., Ford, R., Forrest, E., Fowell, A., Fracanzani, A. L., Francque, S., Freilich, B., Frias, J., Fuchs, M., Fuentes, J., Galambos, M., Gallegos, J., Geerts, A., George, J., Ghali, M., Ghalib, R., Gholam, P., Gines, P., Gitlin, N., Goeser, T., Goff, J., Gordon, S., Gordon, F., Goria, O., Greer, S., Grigorian, A., Gronbaek, H., Guillaume, M., Gunaratnam, N., Halegoua-De Marzio, D., Hameed, B., Hametner, S., Hamilton, J., Hartleb, M., Hassanein, T., Haussinger, D., Hellstern, P., Herring, R., Heurich, E., Hezode, C., Hinrichsen, H., Holland Fischer, P., Horsmans, Y., Huang, J., Jakiche, A., Jeffers, L., Jones, B., Jorge, R., Jorquera, F., Kahraman, A., Kaita, K., Karyotakis, N., Kayali, Z., Kechagias, S., Kepczyk, T., Khalili, M., Khallafi, H., Kluwe, J., Kohli, A., Korenblat, K., Kowdley, K., Krag, A., Krause, R., Kremer, A., Krok, K., Krstic, M., Kugelmas, M., Kumar, S., Labarriere, D., Lai, M., Lampertico, P., Lee, A., Leroy, V., Lidofsky, S., Lim, T. H., Lim, J., Lipkis, D., Little, E., Lonardo, A., Long, M., Lurie, Y., Macedo, G., Makara, M., Maliakkal, B., Manns, M., Manousou, P., Mantry, P., Marchesini, G., Marinho, C., Marotta, P., Marschall, H. -U., Mayo, M., Mccullen, M., Mclaughlin, W., Merriman, R., Modi, A., Molina, E., Montano-Loza, A., Monteverde, C., Moreea, S., Moreno, C., Morisco, F., Mubarak, A., Muellhaupt, B., Mukherjee, S., Muller, T., Nagorni, A., Naik, J., Neff, G., Nevah, M., Newsome, P., Nguyen-Khac, E., Noureddin, M., Oben, J., Orlent, H., Orr, J., Ortiz-Lasanta, G., Ozenne, V., Pandya, P., Paredes, A., Park, J., Patel, J., Patel, K., Uta, M., Patton, H., Peck-Radosavljevic, M., Petta, S., Pianko, S., Piekarska, A., Pimstone, N., Pockros, P., Pol, S., Porayko, M., Poulos, J., Pound, D., Pouzar, J., Presa Ramos, J., Pyrsopoulos, N., Rafiq, N., Muller, K., Ramji, A., Ravinuthala, R., Reddy, C., Reddy K G, G., Reddy K R, K. R., Regenstein, F., Reindollar, R., Riera, A., Rivera Acosta, J., Robaeys, G., Roberts, S., Rodriguez-Perez, F., Romero-Gomez, M., Rubin, R., Rumi, M., Rushbrook, S., Rust, C., Ryan, M., Safadi, R., Said, A., Salminen, K., Samuel, D., Santoro, J., Sanyal, A., Sarkar, S., Schaeffer, C., Schattenberg, J., Schiefke, I., Schiff, E., Schmidt, W., Schneider, J., Schouten, J., Schultz, M., Sebastiani, G., Semela, D., Sepe, T., Sheikh, A., Sheikh, M., Sherman, K., Shibolet, O., Shiffman, M., Siddique, A., Sieberhagen, C., Sigal, S., Sikorska, K., Simon, K., Sinclair, M., Skoien, R., Solis, J., Sood, S., Souder, B., Spivey, J., Stal, P., Stinton, L., Strasser, S., Svorcan, P., Szabo, G., Talal, A., Tam, E., Tetri, B., Thuluvath, P., Tobias, H., Tomasiewicz, K., Torres, D., Trauner, M., Trautwein, C., Tsochatzis, E., Unitt, E., Vargas, V., Varkonyi, I., Veitsman, E., Vespasiani Gentilucci, U., Victor, D., Vierling, J., Vincent, C., Vincze, A., von der Ohe, M., Von Roenn, N., Vuppalanchi, R., Waters, M., Watt, K., Weltman, M., Wieland, A., Wiener, G., Williams A, A., Williams J, J., Wilson, J., Yataco, M., Yoshida, E., Younes, Z., Yuan, L., Zivony, A., Zogg, D., Zoller, H., Zoulim, F., Zuckerman, E., Zuin, M., Younossi, Zobair M, Ratziu, Vlad, Loomba, Rohit, Rinella, Mary, Anstee, Quentin M, Goodman, Zachary, Bedossa, Pierre, Geier, Andrea, Beckebaum, Susanne, Newsome, Philip N, Sheridan, David, Sheikh, Muhammad Y, Trotter, Jame, Knapple, Whitfield, Lawitz, Eric, Abdelmalek, Manal F, Kowdley, Kris V, Montano-Loza, Aldo J, Boursier, Jerome, Mathurin, Philippe, Bugianesi, Elisabetta, Mazzella, Giuseppe, Olveira, Antonio, Cortez-Pinto, Helena, Graupera, Isabel, Orr, David, Gluud, Lise Lotte, Dufour, Jean-Francoi, Shapiro, David, Campagna, Jason, Zaru, Luna, MacConell, Leigh, Shringarpure, Reshma, Harrison, Stephen, Sanyal, Arun J, Abdelmalek, Manal, Abrams, Gary, Aguilar, Humberto, Ahmed, Aijaz, Aigner, Elmar, Aithal, Guruprasad, Ala, Aftab, Alazawi, William, Albillos, Agustin, Allison, Michael, Al-Shamma, Sfa, Andrade, Raul, Andreone, Pietro, Angelico, Mario, Ankoma-Sey, Victor, Anstee, Quentin, Anty, Rodolphe, Araya, Victor, Arenas Ruiz, Juan Ignacio, Arkkila, Perttu, Arora, Marty, Asselah, Tarik, Au, Jennifer, Ayonrinde, Oyekoya, Bailey, Robert Jame, Balakrishnan, Maya, Bambha, Kiran, Bansal, Meena, Barritt, Sidney, Bate, John, Beato, Jorge, Behari, Jaideep, Bellot, Pablo, Ben Ari, Ziv, Bennett, Michael, Berenguer, Marina, Beretta-Piccoli, Benedetta Terziroli, Berg, Thoma, Bonacini, Maurizio, Bonet, Lucia, Borg, Brian, Bourliere, Marc, Bowman, William, Bradley, David, Brankovic, Marija, Braun, Mariu, Bronowicki, Jean-Pierre, Bruno, Savino, Cai, Cindy, Calleja Panero, José Lui, Carey, Elizabeth, Carmiel, Michal, Carrión, Jose Antonio, Cave, Matthew, Chagas, Cristina, Chami, Tawfik, Chang, Alan, Coates, Allan, Cobbold, Jeremy, Corey, Kathleen, Corless, Lynsey, Crespo, Javier, Cruz Pereira, Oscar, de Ledinghen, Victor, deLemos, Andrew, Diago, Moise, Dufour, Jean-Françoi, Dugalic, Predrag, Dunn, Winston, Elkhashab, Magby, Epstein, Michael, Escudero-Garcia, Maria Desamparado, Etzion, Ohad, Evans, Larry, Falcone, Robert, Fernandez, Conrado, Ferreira, Jose, Fink, Scott, Finnegan, Kevin, Firpi-Morell, Roberto, Floreani, Annarosa, Fontanges, Thierry, Ford, Ryan, Forrest, Ewan, Fowell, Andrew, Fracanzani, Anna Ludovica, Francque, Sven, Freilich, Bradley, Frias, Juan, Fuchs, Michael, Fuentes, Javier, Galambos, Michael, Gallegos, Juan, Geerts, Anja, George, Jacob, Ghali, Maged, Ghalib, Reem, Gholam, Pierre, Gines, Pere, Gitlin, Norman, Goeser, Tobia, Goff, John, Gordon, Stuart, Gordon, Frederic, Goria, Odile, Greer, Shaun, Grigorian, Alla, Gronbaek, Henning, Guillaume, Maeva, Gunaratnam, Naresh, Halegoua-De Marzio, Dina, Hameed, Bilal, Hametner, Stephanie, Hamilton, Jame, Hartleb, Marek, Hassanein, Tarek, Häussinger, Dieter, Hellstern, Paul, Herring, Robert, Heurich, Eva, Hezode, Christophe, Hinrichsen, Holger, Holland Fischer, Peter, Horsmans, Yve, Huang, Jonathan, Jakiche, Antoine, Jeffers, Lennox, Jones, Blake, Jorge, Rosa, Jorquera, Francisco, Kahraman, Alisan, Kaita, Kelly, Karyotakis, Nichola, Kayali, Zeid, Kechagias, Stergio, Kepczyk, Thoma, Khalili, Mandana, Khallafi, Hicham, Kluwe, Johanne, Kohli, Anita, Korenblat, Kevin, Kowdley, Kri, Krag, Aleksander, Krause, Richard, Kremer, Andrea, Krok, Karen, Krstic, Miodrag, Kugelmas, Marcelo, Kumar, Sonal, Labarriere, Damien, Lai, Michelle, Lampertico, Pietro, Lee, Alice, Leroy, Vincent, Lidofsky, Steven, Lim, Tina Huey, Lim, Joseph, Lipkis, Donald, Little, Ester, Lonardo, Amadeo, Long, Michelle, Lurie, Yoav, Macedo, Guilherme, Makara, Mihály, Maliakkal, Benedict, Manns, Michael, Manousou, Pinelopi, Mantry, Parvez, Marchesini, Giulio, Marinho, Carla, Marotta, Paul, Marschall, Hanns-Ulrich, Mayo, Marlyn, McCullen, Mark, McLaughlin, William, Merriman, Raphael, Modi, Apurva, Molina, Esther, Montano-Loza, Aldo, Monteverde, Carlo, Moreea, Sulleman, Moreno, Christophe, Morisco, Filomena, Mubarak, Abdullah, Muellhaupt, Beat, Mukherjee, Sandeep, Müller, Tobia, Nagorni, Aleksandar, Naik, Jahnavi, Neff, Guy, Nevah, Moise, Newsome, Philip, Nguyen-Khac, Eric, Noureddin, Mazen, Oben, Jude, Orlent, Han, Orr, Jame, Ortiz-Lasanta, Grisell, Ozenne, Violaine, Pandya, Prashant, Paredes, Angelo, Park, Jame, Patel, Joykumar, Patel, Keyur, Uta, Merle, Patton, Heather, Peck-Radosavljevic, Marku, Petta, Salvatore, Pianko, Stephen, Piekarska, Anna, Pimstone, Neville, Pockros, Paul, Pol, Stanisla, Porayko, Michael, Poulos, John, Pound, David, Pouzar, Joe, Presa Ramos, Jose, Pyrsopoulos, Nikolao, Rafiq, Nila, Muller, Kate, Ramji, Alnoor, Ravinuthala, Ravi, Reddy, Chakradhar, Reddy K G, Gautham, Reddy K R, K. Rajender, Regenstein, Frederic, Reindollar, Robert, Riera, Andre, Rivera Acosta, Jose, Robaeys, Geert, Roberts, Stuart, Rodriguez-Perez, Federico, Romero-Gomez, Manuel, Rubin, Raymond, Rumi, Mariagrazia, Rushbrook, Simon, Rust, Christian, Ryan, Michael, Safadi, Rifaat, Said, Adnan, Salminen, Kimmo, Samuel, Didier, Santoro, John, Sanyal, Arun, Sarkar, Souvik, Schaeffer, Cynthia, Schattenberg, Jörn, Schiefke, Ingolf, Schiff, Eugene, Schmidt, Wolfgang, Schneider, Jeffrey, Schouten, Jeoffrey, Schultz, Michael, Sebastiani, Giada, Semela, David, Sepe, Thoma, Sheikh, Aasim, Sheikh, Muhammad, Sherman, Kenneth, Shibolet, Oren, Shiffman, Mitchell, Siddique, Asma, Sieberhagen, Cyril, Sigal, Samuel, Sikorska, Katarzyna, Simon, Krzysztof, Sinclair, Marie, Skoien, Richard, Solis, Joel, Sood, Siddharth, Souder, Bob, Spivey, Jame, Stal, Per, Stinton, Laura, Strasser, Simone, Svorcan, Petar, Szabo, Gyongzi, Talal, Andrew, Tam, Edward, Tetri, Brent, Thuluvath, Paul, Tobias, Hillel, Tomasiewicz, Krzysztof, Torres, Dawn, Trauner, Michael, Trautwein, Christian, Tsochatzis, Emanuel, Unitt, Esther, Vargas, Victor, Varkonyi, Istvan, Veitsman, Ella, Vespasiani Gentilucci, Umberto, Victor, David, Vierling, John, Vincent, Catherine, Vincze, Aron, von der Ohe, Manfred, Von Roenn, Natasha, Vuppalanchi, Raj, Waters, Michael, Watt, Kymberly, Weltman, Martin, Wieland, Amanda, Wiener, Gregory, Williams A, Alonzo, Williams J, Jeffrey, Wilson, Jason, Yataco, Maria, Yoshida, Eric, Younes, Ziad, Yuan, Liyun, Zivony, Adam, Zogg, Donald, Zoller, Heinz, Zoulim, Fabien, Zuckerman, Eli, Zuin, Massimo, and REGENERATE Study Investigators
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Male ,Biopsy ,Clinical Trial, Phase III ,Administration, Oral ,030204 cardiovascular system & hematology ,Chronic liver disease ,Settore MED/04 ,Biomarkers/analysis ,Gastroenterology ,chemistry.chemical_compound ,0302 clinical medicine ,Liver Function Tests ,Non-alcoholic Fatty Liver Disease ,Clinical endpoint ,Medicine ,030212 general & internal medicine ,610 Medicine & health ,Chenodeoxycholic Acid/administration & dosage ,education.field_of_study ,Liver Function Test ,Research Support, Non-U.S. Gov't ,Fatty liver ,Obeticholic acid ,NASH, OBETICHOLIC ACID ,General Medicine ,Middle Aged ,Multicenter Study ,Randomized Controlled Trial ,Administration ,Female ,Biomarkers ,Chenodeoxycholic Acid ,Double-Blind Method ,Humans ,Human ,Oral ,medicine.medical_specialty ,Population ,Placebo ,03 medical and health sciences ,Research Support, N.I.H., Extramural ,Internal medicine ,Journal Article ,education ,Intention-to-treat analysis ,business.industry ,Biomarker ,Interim analysis ,medicine.disease ,Non-alcoholic Fatty Liver Disease/drug therapy ,chemistry ,Human medicine ,business - Abstract
© 2019 Elsevier Ltd. All rights reserved., Background: Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods: In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH, non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2-F3, or F1 with at least one accompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpoints for the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2-F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings: Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1-F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2-F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1-F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation: Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes.
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- 2019
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29. Insurance Status Correlates with Access to Procedural Therapy for Patients with Early-Stage Hepatocellular Carcinoma: A Retrospective Cohort Study of the National Cancer Database.
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Weaver B, Lidofsky S, Scriver G, and Lester-Coll N
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- Humans, Aged, United States, Medicare, Retrospective Studies, Insurance Coverage, Insurance, Health, Carcinoma, Hepatocellular surgery, Carcinoma, Hepatocellular pathology, Liver Neoplasms therapy, Liver Neoplasms pathology
- Abstract
Purpose: To compare access to specific procedural therapies across insurance types for patients with American Joint Commission on Cancer (AJCC) Stage I or II hepatocellular carcinoma (HCC)., Materials and Methods: Using the National Cancer Database, patients diagnosed with Stage I or II HCC between 2004 and 2019 were identified. Parametric and nonparametric testing was used to compare the rates of procedural modalities and time to therapy across insurance types. Univariate and multivariate logistic regression analyses were used to identify the likelihood of receiving specific procedural therapy based on insurance status., Results: In total, 105,703 patients with AJCC Stage I or II HCC were identified. The rates of ablative therapy were similar across insurance types (18.1% total, 17.2% private insurance, 15.3% uninsured, 18.1% Medicaid, and 18.8% Medicare). In the logistic regression analysis, patients with private insurance were more likely to receive a transplant or undergo resection or procedural therapy of any kind. Patients with Medicare insurance were more likely to undergo ablation (odds ratio, 1.11; 95% confidence interval, 1.07-1.15; P < .001) than those with private insurance., Conclusions: Patients with private insurance were more likely to receive most forms of procedural therapy for early-stage HCC, with the notable exception of ablative therapy, which patients with Medicare were slightly more likely to receive., (Copyright © 2023 SIR. Published by Elsevier Inc. All rights reserved.)
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- 2023
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30. Colorectal Kaposi Sarcoma in an Immunosuppressed Ulcerative Colitis Patient.
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Shah N, Lidofsky S, and Laskiewicz L
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- 2018
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31. Incidence of Crohn's Disease and Ulcerative Colitis in Rhode Island: Report from the Ocean State Crohn's and Colitis Area Registry.
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Shapiro JM, Zoega H, Shah SA, Bright RM, Mallette M, Moniz H, Grabert SA, Bancroft B, Merrick M, Flowers NT, Samad Z, Lidofsky S, LeLeiko NS, and Sands BE
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- Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Colitis, Ulcerative pathology, Crohn Disease pathology, Female, Humans, Incidence, Male, Middle Aged, Registries, Rhode Island epidemiology, Young Adult, Colitis, Ulcerative epidemiology, Crohn Disease epidemiology
- Abstract
Background: Studies describing the incidence of Crohn's disease (CD) and ulcerative colitis (UC) are uncommon in the United States. We sought to determine the incidence of CD and UC in the state of Rhode Island., Methods: The Ocean State Crohn's and Colitis Area Registry is a state-based inception cohort of patients newly diagnosed with inflammatory bowel disease (IBD) in Rhode Island. To confirm a diagnosis of CD, UC, or IBD unclassified (IBDU), the National Institute of Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium criteria were applied in a review of medical records from gastroenterology practices located in the state of Rhode Island and adjacent to the Rhode Island border in Massachusetts and Connecticut. Using population-based data, we determined the statewide incidence of IBD in Rhode Island from 2008 to 2010., Results: A total of 971 Rhode Island residents were diagnosed with IBD, including 444 with CD, 486 with UC, and 41 with IBD unclassified from 2008 to 2010. The overall age- and sex-adjusted IBD incidence was 30.2 (95% confidence interval, 28.3-32.1) per 100,000 persons in this time frame with 13.9, 15.1, and 1.3 per 100,000 diagnosed with CD, UC, and IBD unclassified, respectively. Of the total incident cases in Rhode Island, 30% (n = 291) were enrolled in Ocean State Crohn's and Colitis Area Registry for follow-up., Conclusions: The incidence of IBD in Rhode Island is higher than that previously reported by other population-based cohorts in the United States. Prospective follow-up of individuals enrolled in the community-based Ocean State Crohn's and Colitis Area Registry cohort is ongoing.
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- 2016
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32. Body image dissatisfaction in patients with inflammatory bowel disease.
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Saha S, Zhao YQ, Shah SA, Esposti SD, Lidofsky S, Shapiro J, Leleiko N, Bright R, Law M, Moniz H, Samad Z, Merrick M, and Sands BE
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- Adolescent, Adult, Aged, Cohort Studies, Emotions, Female, Follow-Up Studies, Humans, Inflammatory Bowel Diseases physiopathology, Male, Middle Aged, Prognosis, Registries, Surveys and Questionnaires, Young Adult, Body Image psychology, Inflammatory Bowel Diseases psychology, Patient Satisfaction statistics & numerical data, Quality of Life
- Abstract
Background: Despite the fact that the inflammatory bowel diseases (IBD) and their treatments may affect physical appearance, the effect of IBD on body image is poorly understood. The aims of this study were to determine whether body image dissatisfaction (BID) changes over time in patients with IBD and to examine the demographic and disease-related variables associated with decreased body image., Methods: Adults aged 18 and above in the Ocean State Crohn's and Colitis Area Registry with at least 2 years of follow-up were eligible for this study. All patients were enrolled within 6 months of IBD diagnosis and followed prospectively. BID was assessed using a modified version of the Adapted Satisfaction With Appearance questionnaire. Total Adapted Satisfaction With Appearance scores and 2 subscores were calculated. To assess for changes over time, general linear models for correlated data were used for continuous outcomes, and generalized estimating equations were used for discrete outcomes., Results: Two hundred seventy-four patients were studied. BID was found to be stable over time among men and women with IBD despite overall improvements in disease activity. No differences were found in BID according to IBD subtype. Female gender, greater disease activity, higher symptom burden, longer duration of steroid use, dermatologic and musculoskeletal manifestations of IBD, and ileocolonic disease location among patients with Crohn's disease were associated with greater BID. Greater BID was associated with lower health-related quality of life., Conclusions: BID remains stable in an incident cohort of IBD despite improved disease activity and is associated with lower health-related quality of life.
- Published
- 2015
- Full Text
- View/download PDF
33. Menstrual cycle changes in women with inflammatory bowel disease: a study from the ocean state Crohn's and colitis area registry.
- Author
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Saha S, Zhao YQ, Shah SA, Esposti SD, Lidofsky S, Salih S, Bright R, Law M, Moniz H, Flowers N, Merrick M, and Sands BE
- Subjects
- Adult, Female, Follow-Up Studies, Humans, Oceans and Seas, Prognosis, Prospective Studies, Colitis, Ulcerative physiopathology, Crohn Disease physiopathology, Menstrual Cycle physiology, Registries statistics & numerical data
- Abstract
Background: The effect of the inflammatory bowel diseases (IBD) on menstrual function is largely unknown. The aims of this study were to determine whether changes in menstrual function occur in the year before IBD diagnosis or in the initial years after diagnosis., Methods: Women aged 18 years and older in the Ocean State Crohn's and Colitis Area Registry with at least 2 years of follow-up were eligible for this study. All patients were enrolled within 6 months of IBD diagnosis and followed prospectively. Menstrual cycle characteristics were retrospectively assessed. To assess for changes over time, general linear models for correlated data were used for continuous outcomes, and generalized estimating equations were used for discrete outcomes., Results: One hundred twenty-one patients were studied. Twenty-five percent of patients experienced a change in cycle interval in the year before IBD diagnosis and 21% experienced a change in the duration of flow. Among women with dysmenorrhea, 40% experienced a change in the intensity of their menstrual pain and 31% experienced a change in its duration. Overall cycle regularity increased over time. Quality of life was significantly lower in women without regular cycles across all time points., Conclusions: Changes in menstrual function occur frequently in the year before IBD diagnosis; therefore, screening for menstrual irregularities should be considered in women with newly diagnosed IBD. Patients can be reassured that cycles typically become more regular over time.
- Published
- 2014
- Full Text
- View/download PDF
34. Ingested foreign body in the sigmoid colon: detection and localization by CT colonography.
- Author
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Chang KJ, Schechter S, Vrees M, and Lidofsky S
- Subjects
- Aged, Female, Humans, Colon, Sigmoid, Colonography, Computed Tomographic, Foreign Bodies diagnosis
- Published
- 2012
35. Evaluation of possible inflammatory bowel disease: a survey of Rhode Island physicians.
- Author
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Saha S, Lam M, Roberson E, Shah S, LeLeiko NS, Lidofsky S, Bright R, Flowers N, Merrick M, and Sands BE
- Subjects
- Abdominal Pain etiology, Adult, Aged, Female, Health Care Surveys, Humans, Male, Middle Aged, Physicians, Primary Care, Practice Patterns, Physicians', Primary Health Care, Rhode Island, Inflammatory Bowel Diseases diagnosis
- Abstract
Background: Patients with undiagnosed inflammatory bowel disease (IBD) are often evaluated initially by primary care physicians (PCPs). Despite the frequency with which PCPs evaluate chronic abdominal pain and chronic diarrhea, little is known about how they approach these symptoms., Objectives: To determine the diagnostic practices and referral patterns of PCPs when confronting a patient with potential IBD., Methods: We conducted a mail survey of PCPs practicing in Rhode Island. Clinical vignettes describing patients with chronic abdominal pain and chronic diarrhea were presented. Respondents were asked to indicate how they would evaluate these scenarios and when they would refer to a specialist., Results: 432 PCPs were surveyed; 35.6% responded. Wide variation in PCPs' definitions of chronic abdominal pain and chronic diarrhea was found, with only 26% and 51% of physicians, respectively, defining these symptoms to be chronic per standard definitions. Laboratory testing was found to vary significantly with practice type (p < 0.01 for 2 patient groups). Patient age influenced the ordering of diagnostic imaging (p < 0.0001), while patient gender did not., Conclusions: There is significant variability among PCPs in the threshold after which common gastrointestinal symptoms become chronic as well as in their diagnostic evaluation of these symptoms. This variability may lead to a lag in the diagnosis of IBD and influence patient outcomes.
- Published
- 2012
36. Bone disease in the inflammatory bowel disease population.
- Author
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Smith J and Lidofsky S
- Subjects
- Bone Density, Bone Diseases, Metabolic diagnosis, Bone Diseases, Metabolic etiology, Bone Diseases, Metabolic therapy, Global Health, Humans, Inflammatory Bowel Diseases complications, Inflammatory Bowel Diseases therapy, Bone Diseases, Metabolic epidemiology, Inflammatory Bowel Diseases epidemiology
- Published
- 2009
37. Glucocorticoid-induced osteoporosis in inflammatory bowel disease.
- Author
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Lidofsky S and Smith J
- Subjects
- Bone Density Conservation Agents therapeutic use, Calcium Compounds therapeutic use, Dietary Supplements, Diphosphonates therapeutic use, Glucocorticoids therapeutic use, Humans, Inflammatory Bowel Diseases complications, Osteoporosis therapy, Vitamin D therapeutic use, Glucocorticoids adverse effects, Inflammatory Bowel Diseases drug therapy, Osteoporosis chemically induced
- Abstract
Osteoporosis secondary to glucocorticoid use is a potentially preventable disorder. It is the role of the physician to establish and maintain disease remission, minimize the use of glucocorticoids, and initiate measures to prevent and treat bone loss. The essentials of management include lifestyle modifications, nutritional interventions, and pharmacologic therapies. Bisphosphonates should be used when indicated.
- Published
- 2009
38. Detection and prevention of colon cancer: colonoscopy, virtual colonoscopy, and DNA stool tests.
- Author
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Lidofsky S
- Subjects
- Biomarkers, Tumor analysis, Colorectal Neoplasms genetics, Feces chemistry, Humans, Sensitivity and Specificity, Colonography, Computed Tomographic, Colonoscopy, Colorectal Neoplasms diagnosis
- Published
- 2005
39. Risk of early surgery for Crohn's disease: implications for early treatment strategies.
- Author
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Sands BE, Arsenault JE, Rosen MJ, Alsahli M, Bailen L, Banks P, Bensen S, Bousvaros A, Cave D, Cooley JS, Cooper HL, Edwards ST, Farrell RJ, Griffin MJ, Hay DW, John A, Lidofsky S, Olans LB, Peppercorn MA, Rothstein RI, Roy MA, Saletta MJ, Shah SA, Warner AS, Wolf JL, Vecchio J, Winter HS, and Zawacki JK
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Chi-Square Distribution, Child, Female, Humans, Logistic Models, Male, Middle Aged, New England, Retrospective Studies, Risk Assessment, Risk Factors, Time Factors, Treatment Outcome, Crohn Disease surgery
- Abstract
Objectives: In this study we aimed to define the rate of early surgery for Crohn's disease and to identify risk factors associated with early surgery as a basis for subsequent studies of early intervention in Crohn's disease., Methods: We assembled a retrospective cohort of patients with Crohn's disease diagnosed between 1991 and 1997 and followed for at least 3 yr, who were identified in 16 community and referral-based practices in New England. Chart review was performed for each patient. Details of baseline demographic and disease features were recorded. Surgical history including date of surgery, indication, and procedure were also noted. Risk factors for early surgery (defined as major surgery for Crohn's disease within 3 yr of diagnosis, exclusive of major surgery at time of diagnosis) were identified by univariate analysis. Multiple logistic regression was used to identify independent risk factors., Results: Of 345 eligible patients, 69 (20.1%) required surgery within 3 yr of diagnosis, excluding the 14 patients (4.1%) who had major surgery at the time of diagnosis. Overall, the interval between diagnosis and surgery was short; one half of all patients who required surgery underwent operation within 6 months of diagnosis. Risk factors identified by univariate analysis as significantly associated with early surgery included the following: smoking; disease of small bowel without colonic involvement; nausea and vomiting or abdominal pain on presentation; neutrophil count; and steroid use in the first 6 months. Disease localized to the colon only, blood in the stool, use of 5-aminosalicylate, and lymphocyte count were inversely associated with risk of early surgery. Logistic regression confirmed independent associations with smoking as a positive risk factor and involvement of colon without small bowel as a negative risk factor for early surgery., Conclusions: The rate of surgery is high in the first 3 yr after diagnosis of Crohn's disease, particularly in the first 6 months. These results suggest that improved risk stratification and potent therapies with rapid onset of action are needed to modify the natural history of Crohn's disease.
- Published
- 2003
- Full Text
- View/download PDF
40. Cloning and functional expression of a liver isoform of the small conductance Ca2+-activated K+ channel SK3.
- Author
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Barfod ET, Moore AL, and Lidofsky SD
- Subjects
- Animals, Apamin pharmacology, Calcium metabolism, Carcinoma, Hepatocellular, Cloning, Molecular, Fluorescent Antibody Technique, Hepatocytes chemistry, Humans, Isomerism, Kidney cytology, Liver Neoplasms, Membrane Potentials drug effects, Membrane Potentials physiology, Molecular Sequence Data, Patch-Clamp Techniques, Potassium metabolism, Potassium Channels chemistry, Rats, Sequence Homology, Amino Acid, Small-Conductance Calcium-Activated Potassium Channels, Transfection, Tumor Cells, Cultured, Liver chemistry, Liver metabolism, Potassium Channels genetics, Potassium Channels metabolism, Potassium Channels, Calcium-Activated
- Abstract
Small conductance Ca2+-activated K+ (SK) channels have been cloned from mammalian brain, but little is known about the molecular characteristics of SK channels in nonexcitable tissues. Here, we report the isolation from rat liver of an isoform of SK3. The sequence of the rat liver isoform differs from rat brain SK3 in five amino acid residues in the NH3 terminus, where it more closely resembles human brain SK3. SK3 immunoreactivity was detectable in hepatocytes in rat liver and in HTC rat hepatoma cells. Human embryonic kidney (HEK-293) cells transfected with liver SK3 expressed 10 pS K+ channels that were Ca2+ dependent (EC(50) 630 nM) and were blocked by the SK channel inhibitor apamin (IC(50) 0.6 nM); whole cell SK3 currents inactivated at membrane potentials more positive than -40 mV. Notably, the Ca2+ dependence, apamin sensitivity, and voltage-dependent inactivation of SK3 are strikingly similar to the properties of hepatocellular and biliary epithelial SK channels evoked by metabolic stress. These observations raise the possibility that SK3 channels influence membrane K+ permeability in hepatobiliary cells during liver injury.
- Published
- 2001
- Full Text
- View/download PDF
41. Activation of potassium and chloride channels by tumor necrosis factor alpha. Role in liver cell death.
- Author
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Nietsch HH, Roe MW, Fiekers JF, Moore AL, and Lidofsky SD
- Subjects
- Alkaloids, Animals, Barium pharmacology, Benzophenanthridines, Calcium pharmacology, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Calcium-Calmodulin-Dependent Protein Kinases pharmacology, Chloride Channels drug effects, Chlorides metabolism, Dactinomycin pharmacology, Egtazic Acid pharmacology, Ion Channels agonists, Ion Channels antagonists & inhibitors, Nitrobenzoates pharmacology, Patch-Clamp Techniques, Phenanthridines pharmacology, Potassium metabolism, Potassium Channels drug effects, Protein Kinase C antagonists & inhibitors, Protein Kinase C metabolism, Quinine, Rats, Tumor Cells, Cultured, ortho-Aminobenzoates pharmacology, Apoptosis drug effects, Chloride Channels metabolism, Liver metabolism, Potassium Channels metabolism, Tumor Necrosis Factor-alpha pharmacology
- Abstract
Despite abundant evidence for changes in mitochondrial membrane permeability in tumor necrosis factor (TNF)-mediated cell death, the role of plasma membrane ion channels in this process remains unclear. These studies examine the influence of TNF on ion channel opening and death in a model rat liver cell line (HTC). TNF (25 ng/ml) elicited a 2- and 5-fold increase in K(+) and Cl(-) currents, respectively, in HTC cells. These increases occurred within 5-10 min after TNF exposure and were inhibited either by K(+) or Cl(-) substitution or by K(+) channel blockers (Ba(2+), quinine, 0.1 mm each) or Cl(-) channel blockers (10 microm 5-nitro-2-(3-phenylpropylamino)benzoic acid and 0.1 mm N-phenylanthranilic acid), respectively. TNF-mediated increases in K(+) and Cl(-) currents were each inhibited by intracellular Ca(2+) chelation (5 mm EGTA), ATP depletion (4 units/ml apyrase), and the protein kinase C (PKC) inhibitors chelerythrine (10 micrometer) or PKC 19-36 peptide (1 micrometer). In contrast, currents were not attenuated by the calmodulin kinase II 281-309 peptide (10 micrometer), an inhibitor of calmodulin kinase II. In the presence of actinomycin D (1 micrometer), each of the above ion channel blockers significantly delayed the progression to TNF-mediated cell death. Collectively, these data suggest that activation of K(+) and Cl(-) channels is an early response to TNF signaling and that channel opening is Ca(2+)- and PKC-dependent. Our findings further suggest that K(+) and Cl(-) channels participate in pathways leading to TNF-mediated cell death and thus represent potential therapeutic targets to attenuate liver injury from TNF.
- Published
- 2000
- Full Text
- View/download PDF
42. Severe hepatotoxicity associated with bromfenac sodium.
- Author
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Moses PL, Schroeder B, Alkhatib O, Ferrentino N, Suppan T, and Lidofsky SD
- Subjects
- Adult, Chemical and Drug Induced Liver Injury pathology, Female, Humans, Liver Failure pathology, Analgesics adverse effects, Anti-Inflammatory Agents, Non-Steroidal adverse effects, Benzophenones adverse effects, Bromobenzenes adverse effects, Chemical and Drug Induced Liver Injury etiology, Liver Failure chemically induced
- Abstract
Subacute hepatitis and liver failure occurred in a 40-yr-old woman following a 1-month course of treatment with the nonsteroidal anti-inflammatory drug bromfenac. Serologies for hepatitis A, B, and C were negative, as were antinuclear antibodies and ceruloplasmin. A transjugular liver biopsy demonstrated submassive hepatic necrosis. The clinical course was complicated by encephalopathy, fluid retention, and spontaneous bacterial peritonitis, prompting consideration for liver transplantation. With supportive measures, jaundice and fluid retention resolved over a 3-month period. We conclude that prolonged use of bromfenac was the etiological agent in this case, and that this drug can cause severe hepatotoxicity resulting in liver failure.
- Published
- 1999
- Full Text
- View/download PDF
43. Alanine uptake activates hepatocellular chloride channels.
- Author
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Lidofsky SD and Roman RM
- Subjects
- Animals, Biological Transport, Chloride Channels drug effects, Intracellular Fluid drug effects, Intracellular Fluid physiology, Kinetics, Membrane Potentials drug effects, Membrane Potentials physiology, Potassium Channels drug effects, Potassium Channels physiology, Rats, Tumor Cells, Cultured, Alanine metabolism, Alanine pharmacology, Chloride Channels physiology, Liver Neoplasms, Experimental metabolism
- Abstract
Cells involved in the retrieval and metabolic conversion of amino acids undergo significant increases in size in response to amino acid uptake. The resultant adaptive responses to cell swelling are thought to include increases in membrane K+ and Cl- permeability through activation of volume-sensitive ion channels. This viewpoint is largely based on experimental models of hypotonic swelling, but few mammalian cells experience hypotonic challenge in vivo. Here we have examined volume regulatory responses in a physiological model of cell-swelling alanine uptake in immortalized hepatocytes. Alanine-induced cell swelling was followed by a decrease in cell volume that was temporally associated with an increase in membrane Cl- currents. These currents were dependent both on alanine concentration and Na+, suggesting that currents were stimulated by Na+-coupled alanine uptake. Cl- currents were outwardly rectifying, exhibited an anion permeability sequence of I- > Br- > Cl-, and were inhibited by the Cl- channel blocker 5-nitro-2-(3-phenylpropylamino)benzoic acid, features similar to those reported for a widely distributed class of volume-sensitive anion channels evoked by experimental hypotonic stress. These findings suggest that volume-sensitive anion channels participate in adaptive responses to amino acid uptake and provide such channels with a new physiological context.
- Published
- 1997
- Full Text
- View/download PDF
44. Regulation of cation-selective channels in liver cells.
- Author
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Lidofsky SD, Sostman A, and Fitz JG
- Subjects
- Animals, Patch-Clamp Techniques, Rats, Tumor Cells, Cultured, Calcium metabolism, Ion Channels metabolism, Liver metabolism
- Abstract
In liver cells, cation-selective channels are permeable to Ca2+ and have been postulated to represent a pathway for receptor-mediated Ca2+ influx. This study examines the mechanisms involved in the regulation of these channels in a model liver cell line. Using patch-clamp recording techniques, it is shown that channel open probability is a saturable function of cytosolic [Ca2+], with half-maximal opening at 660 nm. By contrast, channel opening is not affected by membrane voltage or cytosolic pH. In intact cells, reduction of cytosolic [Cl-], a physiological response to Ca2+-mobilizing hormones and cell swelling, is also associated with an increase in channel opening. Finally, channel opening is inhibited by intracellular ATP through a mechanism that does not involve ATP hydrolysis. These findings suggest that opening of cation-selective channels is coupled to the metabolic state of the cell and provides a positive feedback mechanism for regulation of receptor-mediated Na+ and Ca2+ influx.
- Published
- 1997
- Full Text
- View/download PDF
45. Fulminant hepatic failure.
- Author
-
Lidofsky SD
- Subjects
- Emergencies, Hepatic Encephalopathy complications, Hepatic Encephalopathy etiology, Humans, Liver Transplantation, Patient Selection, Hepatic Encephalopathy therapy
- Abstract
Fulminant hepatic failure is a devastating complication of viral hepatitis, hepatotoxic exposures, and a variety of other acute liver diseases. Although this syndrome is associated with high mortality, liver transplantation can be life saving. This article discusses the medical management of fulminant hepatic failure and emphasizes complications, determinants of survival, and patient selection for liver transplantation.
- Published
- 1995
46. Vasopressin increases cytosolic sodium concentration in hepatocytes and activates calcium influx through cation-selective channels.
- Author
-
Lidofsky SD, Xie MH, Sostman A, Scharschmidt BF, and Fitz JG
- Subjects
- Animals, Biological Transport, Cells, Cultured, Cytosol drug effects, Cytosol metabolism, Ion Channels metabolism, Liver cytology, Liver metabolism, Membrane Potentials, Rats, Calcium metabolism, Ion Channels drug effects, Liver drug effects, Sodium metabolism, Vasopressins pharmacology
- Abstract
A variety of hormonal agonists activate transmembrane Na+ and Ca2+ flux in hepatocytes, but the responsible mechanisms are poorly understood. We employed microfluorimetric and patch clamp recording techniques in hepatocytes to determine the effect of the hormone vasopressin on cytosolic Na+ concentration ([Na+]i) and to identify the transmembrane Na+ transport pathways activated by this agonist. Under basal conditions, [Na+]i, measured using the Na(+)-sensitive fluorophore sodium-binding benzofuran isophthalate, averaged 12.1 +/- 1.6 mM. Exposure to vasopressin rapidly increased [Na+]i by 8.3 +/- 0.9 mM. This increase was attributable to activation of Na+ influx. It occurred in the absence of solutes co-transported with Na+ and was not associated with activation of Na+/H+ antiport. In cell-attached membrane patches, vasopressin activated ion channels that carried inward positive current at the resting membrane potential. Further characterization in excised membrane patches revealed two classes of ion channels, with conductances of 16.0 +/- 2.8 and 30.9 +/- 3.1 picosiemens, respectively. Single channel currents reversed near 0 mV, and ion substitution studies demonstrated that each channel type was permeable to Na+, Ca2+, and K+ but not Cl-. These observations in hepatocytes indicate that vasopressin increases [Na+]i and activates cation-selective channels, which likely accounts for vasopressin-activated Na+ and Ca2+ influx.
- Published
- 1993
47. Liver transplantation for fulminant hepatic failure.
- Author
-
Lidofsky SD
- Subjects
- Brain Edema complications, Hepatic Encephalopathy complications, Humans, Multiple Organ Failure complications, Prognosis, Renal Insufficiency complications, Risk Factors, Tissue and Organ Procurement, Hepatic Encephalopathy surgery, Liver Transplantation
- Abstract
In conclusion, the availability of liver transplantation has dramatically advanced the management of fulminant hepatic failure. A major responsibility of the gastroenterologist/hepatologist involved in the care of patients with liver failure is early decision making regarding likelihood of spontaneous recovery and consideration toward referral to a transplantation center. In particular, patients with exposure to drugs or toxins (other than acetaminophen); patients with presumed non-A, non-B hepatitis; children or older patients; patients with prolonged jaundice; profoundly jaundiced patients; or patients with severe coagulopathy should be given the highest consideration for urgent transplantation. Supportive care should take into account the potential complications of bleeding, sepsis, cerebral edema, renal failure, and respiratory failure. Such complications are the major limiting factors that prevent patients with fulminant hepatic failure from undergoing liver transplantation and contribute to the majority of postoperative deaths among patients who undergo transplantation. If these issues are heeded, and in light of emerging therapeutic modalities and surgical innovations, it is anticipated that ongoing improvement of the overall outcome of patients with fulminant hepatic failure will continue to be seen.
- Published
- 1993
48. Intracranial pressure monitoring during liver transplant without venovenous bypass for fulminant hepatic failure.
- Author
-
Prager MC, Washington DE, Lidofsky SD, Kelley SD, and White JD
- Subjects
- Blood Pressure, Humans, Liver Transplantation methods, Monitoring, Intraoperative, Retrospective Studies, Vena Cava, Inferior, Hepatic Encephalopathy physiopathology, Hepatic Encephalopathy surgery, Intracranial Pressure, Liver Transplantation physiology
- Published
- 1993
49. Mechanisms and functional role of intracellular pH regulation in hepatocytes.
- Author
-
Lidofsky SD, Fitz JG, and Scharschmidt BF
- Subjects
- Animals, Bicarbonates metabolism, Chlorides metabolism, Humans, Hydrogen-Ion Concentration, Membrane Potentials, Sodium metabolism, Thermodynamics, Liver metabolism
- Abstract
Intracellular pH influences and is influenced by a diverse array of hepatocellular processes. It is regulated by the concerted action of three plasma membrane H+/HCO3- transporters that serve to buffer against both acidic (Na+/H+ exchange, Na+/HCO3- cotransport) and basic (Cl-/HCO3- exchange) metabolic challenges. The responsiveness of hepatocytes to these challenges is augmented by a regulatory interplay between pH-mediated changes in Vm and electrogenic Na+/HCO3- cotransport to maintain pHi and Vm within a range optimized to serve liver function. The cost is expenditure of metabolic energy to sustain increased activity of the Na+/K+ pump. The benefit is a dynamic servomechanism well-suited to the metabolic demands of hepatocytes, which may be found in future studies to be employed in other metabolically active epithelia as well.
- Published
- 1993
50. Intracranial pressure monitoring and liver transplantation for fulminant hepatic failure.
- Author
-
Lidofsky SD, Bass NM, Prager MC, Washington DE, Read AE, Wright TL, Ascher NL, Roberts JP, Scharschmidt BF, and Lake JR
- Subjects
- Hepatic Encephalopathy physiopathology, Hepatic Encephalopathy surgery, Humans, Monitoring, Intraoperative adverse effects, Monitoring, Physiologic adverse effects, Preoperative Care, Hepatic Encephalopathy therapy, Intracranial Pressure, Liver Transplantation
- Abstract
Cerebral edema and intracranial hypertension, commonly present in fulminant hepatic failure, may lead to brainstem herniation and limit the survival of comatose patients awaiting liver transplantation before a donor organ becomes available. Also, they are likely responsible for postoperative neurological morbidity and mortality. Although intracranial pressure monitoring has been proposed to aid clinical decision making in this setting, its use in the prevention of brainstem herniation preoperatively, in the selection of patients for liver transplantation who have the potential for neurological recovery and in the maintenance of cerebral perfusion during liver transplantation has not been examined in detail. To address these issues, we established a protocol for intracranial pressure monitoring in comatose patients with fulminant hepatic failure as part of their preoperative and intraoperative management. Twenty adults and three children underwent intracranial pressure monitoring. Ten patients required preoperative medical therapy with mannitol, barbiturates or both for a rise in intracranial pressure above 25 mm Hg. Four patients had a sustained lowering of intracranial pressure, three of whom survived hospitalization. Six patients had intracranial hypertension refractory to medical management, were removed from a waiting list for a donor organ and died with brainstem herniation. Of the remaining 17 patients, 3 died of other causes while awaiting a donor organ, 2 recovered spontaneously without neurological sequelae and 12 underwent liver transplantation. All but one patient undergoing liver transplantation had transient intraoperative intracranial hypertension develop, requiring medical treatment. The 12 patients who had transplants recovered neurologically and were discharged from the hospital.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1992
- Full Text
- View/download PDF
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