WorldWideScience

Sample records for infection combination therapy

  1. Vancomycin-Rifampin Combination Therapy Has Enhanced Efficacy against an Experimental Staphylococcus aureus Prosthetic Joint Infection

    Science.gov (United States)

    Niska, Jared A.; Shahbazian, Jonathan H.; Ramos, Romela Irene; Francis, Kevin P.; Bernthal, Nicholas M.

    2013-01-01

    Treatment of prosthetic joint infections often involves a two-stage exchange, with implant removal and antibiotic spacer placement followed by systemic antibiotic therapy and delayed reimplantation. However, if antibiotic therapy can be improved, one-stage exchange or implant retention may be more feasible, thereby decreasing morbidity and preserving function. In this study, a mouse model of prosthetic joint infection was used in which Staphylococcus aureus was inoculated into a knee joint containing a surgically placed metallic implant extending from the femur. This model was used to evaluate whether combination therapy of vancomycin plus rifampin has increased efficacy compared with vancomycin alone against these infections. On postoperative day 7, vancomycin with or without rifampin was administered for 6 weeks with implant retention. In vivo bioluminescence imaging, ex vivo CFU enumeration, X-ray imaging, and histologic analysis were carried out. We found that there was a marked therapeutic benefit when vancomycin was combined with rifampin compared with vancomycin alone. Taken together, our results suggest that the mouse model used could serve as a valuable in vivo preclinical model system to evaluate and compare efficacies of antibiotics and combinatory therapy for prosthetic joint infections before more extensive studies are carried out in human subjects. PMID:23917317

  2. Antimicrobial photodynamic therapy combined with conventional endodontic treatment to eliminate root canal biofilm infection.

    Science.gov (United States)

    Garcez, Aguinaldo S; Ribeiro, Martha S; Tegos, George P; Núñez, Silvia C; Jorge, Antonio O C; Hamblin, Michael R

    2007-01-01

    To compare the effectiveness of antimicrobial photodynamic therapy (PDT), standard endodontic treatment and the combined treatment to eliminate bacterial biofilms present in infected root canals. Ten single-rooted freshly extracted human teeth were inoculated with stable bioluminescent Gram-negative bacteria, Proteus mirabilis and Pseudomonas aeruginosa to form 3-day biofilms in prepared root canals. Bioluminescence imaging was used to serially quantify bacterial burdens. PDT employed a conjugate between polyethylenimine and chlorin(e6) as the photosensitizer (PS) and 660-nm diode laser light delivered into the root canal via a 200-micro fiber, and this was compared and combined with standard endodontic treatment using mechanical debridement and antiseptic irrigation. Endodontic therapy alone reduced bacterial bioluminescence by 90% while PDT alone reduced bioluminescence by 95%. The combination reduced bioluminescence by >98%, and importantly the bacterial regrowth observed 24 hours after treatment was much less for the combination (Ptreatment. Bioluminescence imaging is an efficient way to monitor endodontic therapy. Antimicrobial PDT may have a role to play in optimized endodontic therapy. (c) 2006 Wiley-Liss, Inc.

  3. The effect of combined antiretroviral therapy on the overall mortality of HIV-infected individuals

    NARCIS (Netherlands)

    Phillips, A. N.; Gilson, R.; Easterbrook, P.; Fisher, M.; Gazzard, B.; Johnson, M.; Walsh, J.; Leen, C.; Orkin, C.; Anderson, J.; Pillay, D.; Delpech, V.; Schwenk, A.; Dunn, D.; Gompels, M.; Hill, T.; Porter, K.; Babiker, A.; Sabin, C.; Waters, A.; Crates, D.; Mohamed-Saad, S.; Perry, N.; Pullin, A.; Churchill, D.; Harris, W.; Nelson, M.; Asboe, D.; Bulbeck, S.; Mandalia, S.; Clarke, J.; Dodds, J.; Rider, A.; Youle, M.; Lampe, F.; Smith, C.; Gumley, H.; Chaloner, C.; Ismajani, D.; Weber, J.; Cashin, S.; Kemble, C.; Mackie, N.; Thomas, R.; Jones, K.; Gann, S.; Wilson, A.; Ainsworth, J.; de Wolf, F.; Bezemer, D. O.; Gras, L. A. J.; Kesselring, A. M.; van Sighem, A. I.; Smit, C.; Zhang, S.; Zaheri, S.; Prins, J. M.; Bos, J. C.; Eeftinck-Schattenkerk, J. K. M.; Geerlings, S. E.; Godfried, M. H.; Lange, J. M. A.; van der Meer, J. T. M.; Nellen, F. J. B.; Olszyna, D. P.; van der Poll, M.; Reiss, P.; Sankatsing, S. U. C.; Steingrover, R.; van der Valk, M.; Vermeulen, J. N.; Vrouenraets, S. M. E.; van Vugt, M.; Wit, F. W. M. N.; Schreij, G.; van der Geest, S.; Oude Lashof, A.; Lowe, S.; Verbon, A.; Kuijpers, T. W.; Pajkrt, D.; Scherpbier, H. J.; van der Ende, M. E.; Bax, H.; van der Feltz, M.; Gelinck, L. B. S.; Nouwen, J. L.; Rijnders, B. J. A.; de Ruiter, E. D.; Slobbe, L.; Schurink, C. A. M.; de Vries, T. E. M. S.; Driessen, G.; van der Flier, M.; Hartwig, N. G.; Branger, J.; Kauffmann, R. H.; Schippers, E. F.; Groeneveld, P. H. P.; Alleman, M. A.; ten Kate, R. W.; Soetekouw, R.; Kroon, F. P.; Arend, S. M.; de Boer, M. G. J.; van den Broek, P. J.; van Dissel, J. T.; van Nieuwkoop, C.; den Hollander, J. G.; Bronsveld, W.; Vriesendorp, R.; Jeurissen, F. J. F.; Leyten, E. M. S.; van Houte, D.; Polée, M. B.; ten Napel, C. H. H.; Kootstra, G. J.; Brinkman, K.; van den Berk, G. E. L.; Blok, W. L.; Frissen, P. H. J.; Schouten, W. E. M.; van Eeden, A.; Verhagen, D. W. M.; Mulder, J. W.; van Gorp, E. C. M.; Mairuhu, A. T. A.; Wagenaar, J.; Juttmann, J. R.; van Kasteren, M. E. E.; Veenstra, J.; Vasmel, W. L. E.; Koopmans, P. P.; Brouwer, A. M.; Dofferhoff, A. S. M.; de Groot, R.; ter Hofstede, H. J. M.; Keuter, M.; van der Ven, A. J. A. M.; Sprenger, H. G.; van Assen, S.; van Leeuwen, J. T. M.; Stek, C. J.; Doedens, R.; Scholvinck, E. H.; Hoepelman, I. M.; Schneider, M. M. E.; Bonten, M. J. M.; Ellerbroek, P. M.; Jaspers, C. A. J. J.; Maarschalk-Ellerbroek, L. J.; Oosterheert, J. J.; Peters, E. J. G.; Mudrikova, T.; Wassenberg, M. W. M.; Weijer, S.; Geelen, S. P. M.; Wolfs, T. F. W.; Danner, S. A.; van Agtmael, M. A.; Bierman, W. F. W.; Claessen, F. A. P.; Hillebrand, M. E.; de Jong, E. V.; Kortmann, W.; Perenboom, R. M.; bij de Vaate, E. A.; Richter, C.; van der Berg, J.; Gisolf, E. H.; Tanis, A. A.; Duits, A. J.; Winkel, K.; Elisabeth, S. T.; Abgrall, S.; Barin, F.; Bentata, M.; Billaud, E.; Boué, F.; Burty, C.; Cabié, A.; Costagliola, D.; Cotte, L.; de Truchis, P.; Duval, X.; Duvivier, C.; Enel, P.; Fredouille-Heripret, L.; Gasnault, J.; Gaud, C.; Gilquin, J.; Grabar, S.; Katlama, C.; Khuong, M. A.; Lang, J. M.; Lascaux, A. S.; Launay, O.; Mahamat, A.; Mary-Krause, M.; Matheron, S.; Meynard, J. L.; Pavie, J.; Pialoux, G.; Pilorgé, F.; Poizot-Martin, I.; Pradier, C.; Reynes, J.; Rouveix, E.; Simon, A.; Tattevin, P.; Tissot-Dupont, H.; Viard, J. P.; Viget, N.; Salomon, Valérie; Jacquemet, N.; Guiguet, M.; Lanoy, E.; Liévre, L.; Selinger-Leneman, H.; Lacombe, J. M.; Potard, V.; Bricaire, F.; Herson, S.; Desplanque, N.; Girard, P. M.; Meyohas, M. C.; Picard, O.; Cadranel, J.; Mayaud, C.; Clauvel, J. P.; Decazes, J. M.; Gerard, L.; Molina, J. M.; Diemer, M.; Sellier, P.; Honoré, P.; Jeantils, V.; Tassi, S.; Mechali, D.; Taverne, B.; Berthé, H.; Dupont, C.; Chandemerle, C.; Mortier, E.; Tisne-Dessus, D.; Weiss, L.; Salmon, D.; Auperin, I.; Roudière, L.; Fior, R.; Delfraissy, J. F.; Goujard, C.; Jung, C.; Lesprit, P. H.; Vittecoq, D.; Fraisse, P.; Rey, D.; Beck-Wirth, G.; Stahl, J. P.; Lecercq, P.; Gourdon, F.; Laurichesse, H.; Fresard, A.; Lucht, F.; Bazin, C.; Verdon, R.; Chavanet, P.; Arvieux, C.; Michelet, C.; Choutet, P.; Goudeau, A.; Maître, M. F.; Hoen, B.; Eglinger, P.; Faller, J. P.; Borsa-Lebas, F.; Caron, F.; Daures, J. P.; May, T.; Rabaud, C.; Berger, J. L.; Rémy, G.; Arlet-Suau, E.; Cuzin, L.; Massip, P.; Legrand, M. F. Thiercelin; Pontonnier, G.; Yasdanpanah, Y.; Dellamonica, P.; Pugliese, P.; Aleksandrowicz, K.; Quinsat, D.; Ravaux, I.; Delmont, J. P.; Moreau, J.; Gastaut, J. A.; Retornaz, F.; Soubeyrand, J.; Galinier, A.; Ruiz, J. M.; Allegre, T.; Blanc, P. A.; Bonnet-Montchardon, D.; Lepeu, G.; Granet-Brunello, P.; Esterni, J. P.; Pelissier, L.; Cohen-Valensi, R.; Nezri, M.; Chadapaud, S.; Laffeuillade, A.; Raffi, F.; Boibieux, A.; Peyramond, D.; Livrozet, J. M.; Touraine, J. L.; Trepo, C.; Strobel, M.; Bissuel, F.; Pradinaud, R.; Sobesky, M.; Contant, M.; Aebi, C.; Battegay, M.; Bernasconi, E.; Böni, J.; Brazzola, P.; Bucher, H. C.; Bürgisser, P. H.; Calmy, A.; Cattacin, S.; Cavassini, M.; Cheseaux, J.-J.; Drack, G.; Dubs, R.; Egger, M.; Elzi, L.; Fischer, M.; Flepp, M.; Fontana, A.; Francioli, P.; Furrer, H. J.; Fux, C.; Gayet-Ageron, A.; Gerber, S.; Gorgievski, M.; Günthard, H.; Gyr, T. H.; Hirsch, H.; Hirschel, B.; Hösli, I.; Hüsler, M.; Kaiser, L.; Kahlert, C. H.; Karrer, U.; Kind, C.; Klimkait, T. H.; Ledergerber, B.; Martinetti, G.; Martinez, B.; Müller, N.; Nadal, D.; Paccaud, F.; Pantaleo, G.; Raio, L.; Rauch, A.; Regenass, S.; Rickenbach, M.; Rudin, C.; Schmid, P.; Schultze, D.; Schüpbach, J.; Speck, R.; Taffé, P.; Telenti, A.; Trkola, A.; Vernazza, P.; Weber, R.; Wyler, C.-A.; Yerly, S.; Casabona, J.; Miró, J. M.; Alquézar, A.; Isern, V.; Esteve, A.; Podzamczer, D.; Murillas, J.; Gatell, J. M.; Agüero, F.; Tural, C.; Clotet, B.; Ferrer, E.; Riera, M.; Segura, F.; Navarro, G.; Force, L.; Vilaró, J.; Masabeu, A.; García, I.; Guadarrama, M.; Romero, A.; Agustí, C.; Montoliu, A.; Ortega, N.; Lazzari, E.; Puchol, E.; Sanchez, M.; Blanco, J. L.; Garcia-Alcaide, F.; Martínez, E.; López-Dieguez, M.; García-Goez, J. F.; Sirera, G.; Romeu, J.; Jou, A.; Negredo, E.; Miranda, C.; Capitan, M. C.; Olmo, M.; Barragan, P.; Saumoy, M.; Bolao, F.; Cabellos, C.; Peña, C.; Sala, M.; Cervantes, M.; Amengual, M. J.; Navarro, M.; Penelo, E.; Berenguer, J.; del Amo, J.; García, F.; Gutiérrez, F.; Labarga, P.; Moreno, S.; Muñoz, M. A.; Caro-Murillo, A. M.; Sobrino, P.; Jarrín, I.; Sirvent, J. L. Gómez; Rodríguez, P.; Alemán, M. R.; Alonso, M. M.; López, A. M.; Hernández, M. I.; Soriano, V.; Barreiro, P.; Medrano, J.; Rivas, P.; Herrero, D.; Blanco, F.; Vispo, M. E.; Martín, L.; Ramírez, G.; de Diego, M.; Rubio, R.; Pulido, F.; Moreno, V.; Cepeda, C.; Hervás, R. I.; Iribarren, J. A.; Arrizabalaga, J.; Aramburu, M. J.; Camino, X.; Rodríguez-Arrondo, F.; von Wichmann, M. A.; Pascual, L.; Goenaga, M. A.; Masiá, M.; Ramos, J. M.; Padilla, S.; Sánchez-Hellín, V.; Bernal, E.; Escolano, C.; Montolio, F.; Peral, Y.; López, J. C.; Miralles, P.; Cosín, J.; Sánchez, M.; Gutiérrez, I.; Ramírez, M.; Padilla, B.; Vidal, F.; Sanjuan, M.; Peraire, J.; Veloso, S.; Viladés, C.; López-Dupla, M.; Olona, M.; Vargas, M.; Aldeguer, J. L.; Blanes, M.; Lacruz, J.; Salavert, M.; Montero, M.; Cuéllar, S.; de los Santos, I.; Sanz, J.; Oteo, J. A.; Blanco, J. R.; Ibarra, V.; Metola, L.; Sanz, M.; Pérez-Martínez, L.; Sola, J.; Uriz, J.; Castiello, J.; Reparaz, J.; Arriaza, M. J.; Irigoyen, C.; Antela, A.; Casado, J. L.; Dronda, F.; Moreno, A.; Pérez, M. J.; López, D.; Gutiérrez, C.; Hernández, B.; Pumares, M.; Martí, P.; García, L.; Page, C.; Hernández, J.; Peña, A.; Muñoz, L.; Parra, J.; Viciana, P.; Leal, M.; López-Cortés, L. F.; Trastoy, M.; Mata, R.; Justice, A. C.; Fiellin, D. A.; Rimland, D.; Jones-Taylor, C.; Oursler, K. A.; Titanji, R.; Brown, S.; Garrison, S.; Rodriguez-Barradas, M.; Masozera, N.; Goetz, M.; Leaf, D.; Simberkoff, M.; Blumenthal, D.; Leung, J.; Butt, A.; Hoffman, E.; Gibert, C.; Peck, R.; Mattocks, K.; Braithwaite, S.; Brandt, C.; Bryant, K.; Cook, R.; Conigliaro, J.; Crothers, K.; Chang, J.; Crystal, S.; Day, N.; Erdos, J.; Freiberg, M.; Kozal, M.; Gandhi, N.; Gaziano, M.; Gerschenson, M.; Good, B.; Gordon, A.; Goulet, J. L.; Hernán, M. A.; Kraemer, K.; Lim, J.; Maisto, S.; Miller, P.; Mole, L.; O'Connor, P.; Papas, R.; Robins, J. M.; Rinaldo, C.; Roberts, M.; Samet, J.; Tierney, B.; Whittle, J.; Phillips, A.; Brettle, R.; Darbyshire, J.; Fidler, S.; Goldberg, D.; Hawkins, D.; Jaffe, H.; McLean, K.; Porter, Kholoud; Cursley, Adam; Ewings, Fiona; Fairbrother, Keith; Gnatiuc, Louisa; Lodi, Sara; Murphy, Brendan; Douglas, G.; Kennedy, N.; Pritchard, J.; Andrady, U.; Gwynedd, Ysbyty; Rajda, N.; Maw, R.; McKernan, S.; Drake, S.; Gilleran, G.; White, D.; Ross, J.; Toomer, S.; Hewart, R.; Wilding, H.; Woodward, R.; Dean, G.; Heald, L.; Horner, P.; Glover, S.; Bansaal, D.; Eduards, S.; Carne, C.; Browing, M.; Das, R.; Stanley, B.; Estreich, S.; Magdy, A.; O'Mahony, C.; Fraser, P.; Hayman, B.; Jebakumar, S. P. R.; Joshi, U.; Ralph, S.; Wade, A.; Mette, R.; Lalik, J.; Summerfield, H.; El-Dalil, A.; France, A. J.; White, C.; Robertson, R.; Gordon, S.; McMillan, S.; Morris, S.; Lean, C.; Vithayathil, K.; McLean, L.; Winter, A.; Gale, D.; Jacobs, S.; Tayal, S.; Short, L.; Green, S.; Williams, G.; Sivakumar, K.; Bhattacharyya, D. N.; Monteiro, E.; Minton, J.; Dhar, J.; Nye, F.; DeSouza, C. B.; Isaksen, A.; McDonald, L.; Franca, A.; William, L.; Jendrulek, I.; Shaunak, S.; El-Gadi, S.; Easterbrook, P. J.; Mazhude, C.; Johnstone, R.; Fakoya, A.; Mchale, J.; Kegg, S.; Mitchell, S.; Byrne, P.; Rice, P.; Mullaney, S. A.; McCormack, S.; David, D.; Melville, R.; Phillip, K.; Balachandran, T.; Mabey-Puttock, S.; Sukthankar, A.; Murphy, C.; Wilkins, E.; Ahmad, S.; Haynes, J.; Evans, E.; Ong, E.; Grey, R.; Meaden, J.; Bignell, C.; Loay, D.; Peacock, K.; Girgis, M. R.; Morgan, B.; Palfreeman, A.; Wilcox, J.; Tobin, J.; Tucker, L.; Saeed, A. M.; Chen, F.; Deheragada, A.; Williams, O.; Lacey, H.; Herman, S.; Kinghorn, D.; Devendra, S. V.; Wither, J.; Dawson, S.; Rowen, D.; Harvey, J.; Bridgwood, A.; Singh, G.; Chauhan, M.; Kellock, D.; Young, S.; Dannino, S.; Kathir, Y.; Rooney, G.; Currie, J.; Fitzgerald, M.; Devendra, S.; Keane, F.; Booth, G.; Green, T.; Arumainayyagam, J.; Chandramani, S.; Rajamanoharan, S.; Robinson, T.; Curless, E.; Gokhale, R.; Tariq, A.; Luzzi, G.; Fairley, I.; Wallis, F.; Smit, E.; Ward, F.; Morlat, P.; Bonarek, M.; Bonnet, F.; Nouts, C.; Louis, J.; Reliquet, V.; Sauser, F.; Biron, C.; Mounoury, O.; Hue, H.; Brosseau, D.; Ghosn, J.; Rannou, M. T.; Bergmann, J. F.; Badsi, E.; Rami, A.; Parrinello, M.; Samanon-Bollens, D.; Campa, P.; Tourneur, M.; Desplanques, N.; Jeanblanc, F.; Chiarello, P.; Makhloufi, D.; Blanc, A. P.; Allègre, T.; Baillat, V.; Lemoing, V.; de Boever, C. Merle; Tramoni, C.; Sobesky, G.; Abel, S.; Beaujolais, V.; Slama, L.; Chakvetadze, C.; Berrebi, V.; Yeni, P.; Bouvet, E.; Fournier, I.; Gerbe, J.; Koffi, K.; Augustin-Normand, C.; Miailhes, P.; Thoirain, V.; Brochier, C.; Souala, F.; Ratajczak, M.; Beytoux, J.; Jacomet, C.; Morelon, S.; Olivier, C.; Lortholary, O.; Dupont, B.; Maignan, A.; Ragnaud, J. M.; Raymond, I.; Leport, C.; Jadand, C.; Jestin, C.; Longuet, P.; Boucherit, S.; Sereni, D.; Lascoux, C.; Prevoteau, F.; Sobel, A.; Levy, Y.; Lelièvre, J. D.; Dominguez, S.; Dumont, C.; Aumaître, H.; Delmas, B.; Saada, M.; Medus, M.; Guillevin, L.; Tahi, T.; Yazdanpanah, Y.; Pavel, S.; Marien, M. C.; Drenou, B.; Beck, C.; Benomar, M.; Tubiana, R.; Mohand, H. Ait; Chermak, A.; Abdallah, S. Ben; Touam, F.; Drobacheff, C.; Folzer, A.; Obadia, M.; Prudhomme, L.; Bonnet, E.; Balzarin, F.; Pichard, E.; Chennebault, J. M.; Fialaire, P.; Loison, J.; Galanaud, P.; Bornarel, D.; Six, M.; Ferret, P.; Batisse, D.; Gonzales-Canali, G.; Devidas, A.; Chevojon, P.; Turpault, I.; Lafeuillade, A.; Cheret, A.; Philip, G.; Morel, P.; Timsit, J.; Amirat, N.; Brancion, C.; Cabane, J.; Tredup, J.; Stein, A.; Ravault, I.; Chavanet, C.; Buisson, M.; Treuvetot, S.; Nau, P.; Bastides, F.; Boyer, L.; Wassoumbou, S.; Oksenhendeler, E.; Gérard, L.; Bernard, L.; Domart, Y.; Merrien, D.; Belan, A. Greder; Gayraud, M.; Bodard, L.; Meudec, A.; Beuscart, C.; Daniel, C.; Pape, E.; Vinceneux, P.; Simonpoli, A. M.; Zeng, A.; Fournier, L.; Fuzibet, J. G.; Sohn, C.; Rosenthal, E.; Quaranta, M.; Chaillou, S.; Sabah, M.; Audhuy, B.; Schieber, A.; Moreau, P.; Niault, M.; Vaillant, O.; Huchon, G.; Compagnucci, A.; Szmania, I. De Lacroix; Richier, L.; Lamaury, I.; Saint-Dizier, F.; Garipuy, D.; Drogoul, M. P.; Martin, I. Poizot; Fabre, G.; de Cursay, G. Lambert; Abraham, B.; Perino, C.; Lagarde, P.; David, F.; Roche-Sicot, J.; Saraux, J. L.; Leprêtre, A.; Fampin, B.; Uludag, A.; Morin, A. S.; Bletry, O.; Zucman, D.; Regnier, A.; Girard, J. J.; Quinsat, D. T.; Heripret, L.; Grihon, F.; Houlbert, D.; Ruel, M.; Chemlal, K.; Debab, Y.; Tremollieres, F.; Perronne, V.; Slama, B.; Perré, P.; Miodovski, C.; Guermonprez, G.; Dulioust, A.; Boudon, P.; Malbec, D.; Patey, O.; Semaille, C.; Deville, J.; Remy, G.; Béguinot, I.; Boue, F.; Chambrin, V.; Pignon, C.; Estocq, G. A.; Levy, A.; Duracinsky, M.; Le Bras, P.; Ngussan, M. S.; Peretti, D.; Medintzeff, N.; Lambert, T.; Segeral, O.; Lezeau, P.; Laurian, Y.; Piketty, C.; Karmochkine, M.; Eliaszewitch, M.; Jayle, D.; Tisne- Dessus, D.; Kazatchkine, M.; Colasante, U.; Nouaouia, W.; Vilde, J. L.; Bollens, D.; Binet, D.; Diallo, B.; Fonquernie, L.; Lagneau, J. L.; Pietrie, M. P.; Sicard, D.; Stieltjes, N.; Michot, J.; Bourdillon, F.; Lelievre, J. D.; Obenga, G.; Escaut, L.; Bolliot, C.; Schneider, L.; Iguertsira, M.; Tomei, C.; Dhiver, C.; Dupont, H. Tissot; Vallon, A.; Gallais, J.; Gallais, H.; Durant, J.; Mondain, V.; Perbost, I.; Cassuto, J. P.; Karsenti, J. M.; Venti, H.; Ceppi, C.; Krivitsky, J. A.; Bouchaud, O.; Honore, P.; Delgado, J.; Rouzioux, C.; Burgard, M.; Boufassa, L.; Peynet, J.; Hoyos, S. Pérez; Ferreros, I.; Hurtado, I.; González, C.; Caro, A. M.; Muga, R.; Sanvicens, A.; Tor, J.; del Romero, J.; Raposo, P.; Rodríguez, C.; García, Soledad; Alastrue, I.; Belda, J.; Trullen, P.; Fernández, E.; Santos, C.; Tasa, T.; Zafra, T.; Guerrero, R.; Marco, A.; Quintana, M.; Ruiz, I.; Nuñez, R.; Pérez, R.; Castilla, J.; Guevara, M.; de Mendoza, C.; Zahonero, N.

    2010-01-01

    OBJECTIVE: To estimate the effect of combined antiretroviral therapy (cART) on mortality among HIV-infected individuals after appropriate adjustment for time-varying confounding by indication. DESIGN: A collaboration of 12 prospective cohort studies from Europe and the United States (the HIV-CAUSAL

  4. Combination antibiotic therapy for the treatment of infective endocarditis due to enterococci.

    Science.gov (United States)

    Leone, Sebastiano; Noviello, Silvana; Esposito, Silvano

    2016-06-01

    Enterococci are common causes of infective endocarditis (IE) in both health care and community-based setting. Enterococcal IE requires bactericidal therapy for an optimal outcome. For decades, cell-wall-active antimicrobial agents (penicillins or vancomycin) in combination with aminoglycosides were the cornerstone of the treatment; however, the emergence of antibiotic resistance has significantly reduced the efficacy of these regimens. Data for this review were identified by searches of MEDLINE and references from relevant articles on antibiotic combination regimens for the treatment of enterococcal IE. Abstracts presented in scientific conferences were not searched for. New effective and safe combination treatments, including double-β-lactam and daptomycin/β-lactam combination, are proving useful for the management of IE due to enterococci.

  5. Successful recovery of infective endocarditis-induced rapidly progressive glomerulonephritis by steroid therapy combined with antibiotics: a case report

    Directory of Open Access Journals (Sweden)

    Kikkawa Ryuichi

    2004-12-01

    Full Text Available Abstract Background The mortality rate among patients with infective endocarditis, especially associated with the presence of complications or coexisting conditions such as renal failure and the use of combined medical and surgical therapy remains still high. Prolonged parenteral administration of a bactericidal antimicrobial agent or combination of agents is usually recommended, however, the optimal therapy for infective endocarditis associated with renal injury is not adequately defined. Case presentation Patient was a 24-years old man who presented to our hospital with fever, fatigue, and rapidly progressive glomerulonephritis. He had a history of ventricular septum defect (VSD. A renal biopsy specimen revealed crescentic glomerulonephritis and echocardiogram revealed VSD with vegetation on the tricuspid valve. Specimens of blood demonstrated Propionibacterium Acnes. The intensive antibiotic therapy with penicillin G was started without clinical improvement of renal function or resolution of fever over the next 7 days. After the short-term treatment of low dose of corticosteroid combined with continuous antibiotics, high fever and renal insufficiency were dramatically improved. Conclusion Although renal function in our case worsened despite therapy with antibiotics, a short-term and low dose of corticosteroid therapy with antibiotics was able to recover renal function and the patient finally underwent tricuspid valve-plasty and VSD closure. We suggest that the patients with rapidly progressive glomerulonephritis associated with infective endocarditis might be treated with a short-term and low dose of corticosteroid successfully.

  6. Hepatitis B virus prevalence and vaccine response in HIV-infected children and adolescents on combination antiretroviral therapy in Kigali, Rwanda

    NARCIS (Netherlands)

    Mutwa, Philippe R.; Boer, Kimberly R.; Rusine, John B.; Muganga, Narcisse; Tuyishimire, Diane; Reiss, Peter; Lange, Joep M. A.; Geelen, Sibyl P. M.

    2013-01-01

    The aim of this study was to determine the prevalence of hepatitis B virus (HBV) infection in a cohort of HIV-infected Rwandan children and adolescents on combination antiretroviral therapy (cART), and the success rate of HBV vaccination in those children found to be HBV negative. HIV-infected

  7. Health-related quality of life of HIV-infected adults receiving combination antiretroviral therapy in Addis Ababa

    NARCIS (Netherlands)

    Mekuria, Legese A.; Sprangers, Mirjam A. G.; Prins, Jan M.; Yalew, Alemayehu W.; Nieuwkerk, Pythia T.

    2015-01-01

    Health-related quality of life (HRQoL) is an important outcome measure among HIV-infected patients receiving combination antiretroviral therapy (cART), but has not been studied extensively in resource-limited settings. Insight in the predictors or correlates of poor HRQoL may be helpful to identify

  8. Is there really no benefit to combination therapy with colistin?

    Science.gov (United States)

    Pogue, Jason M; Kaye, Keith S

    2013-09-01

    Despite many theoretical and in vitro advantages, clinical data comparing combination therapy with colistin + rifampicin to colistin alone for infection due to extremely-drug resistant (XDR) Acinetobacter baumanni are scarce and limited by small numbers and/or low quality evidence. This article represents the first large, randomized, controlled, prospective study comparing colistin monotherapy and combination therapy. The reviewed article found no difference in all cause or infection related mortality, though there was an improved rate of microbiological clearance in the combination therapy arm. This study adds important new data to the literature and sets the stage for future studies that can be designed to overcome the limitations of this study, which are discussed in detail below. Based on this study, we cannot say definitively that combination therapy is not warranted for treatment of invasive infection due to A. baumannii, but the results do suggest that rifampicin is not an ideal agent to be combined with colistin.

  9. Combination antiretroviral therapy and cancer risk

    DEFF Research Database (Denmark)

    Borges, Álvaro H

    2017-01-01

    PURPOSE OF REVIEW: To review the newest research about the effects of combination antiretroviral therapy (cART) on cancer risk. RECENT FINDINGS: HIV+ persons are at increased risk of cancer. As this risk is higher for malignancies driven by viral and bacterial coinfections, classifying malignanci......ART initiation in reducing cancer risk, understand the relationship between long-term cART exposure and cancer incidence and assess whether adjuvant anti-inflammatory therapies can reduce cancer risk during treated HIV infection.......PURPOSE OF REVIEW: To review the newest research about the effects of combination antiretroviral therapy (cART) on cancer risk. RECENT FINDINGS: HIV+ persons are at increased risk of cancer. As this risk is higher for malignancies driven by viral and bacterial coinfections, classifying malignancies...... into infection-related and infection-unrelated has been an emerging trend. Cohorts have detected major reductions in the incidence of Kaposi sarcoma and non-Hodgkin lymphoma (NHL) following cART initiation among immunosuppressed HIV+ persons. However, recent randomized data indicate that cART reduces risk...

  10. [Clinical usefulness of the combined empirical therapy with flomoxef and fosfomycin for intractable respiratory tract infections. With a background of increasing MRSA incidence].

    Science.gov (United States)

    Shimada, K; Kudoh, S; Hayashi, I; Shishido, H; Fukuchi, Y; Suzuki, H; Oritsu, M; Nakada, K; Sano, Y; Goto, H

    1994-10-01

    We conducted a multicenter trial to determine the clinical usefulness of the combined therapy with flomoxef (FMOX) and fosfomycin (FOM) (FF therapy) as an empirical therapy in the treatment of intractable respiratory tract infections, because FF therapy has clinically been proved to be very useful for the treatment of severe infections including MRSA infections. The overall efficacy rate of FF therapy was 69.2%. The efficacy rate for "pneumonia/lung abscess," which occupy the largest portions of respiratory tract infections, was 70.0%, showing a statistically significant difference from the efficacy rate for FMOX alone (56.7%) found in a previous study (P = 0.09 by chi-squared test). Although MRSA was eradicated in only 3 cases (37.5%) including superinfection cases, of 8 patients, from whom MRSA had been isolated as causative organisms, none of our patients were superinfected with MRSA. Thus it has been concluded that FF therapy is clinically very useful when used as an empirical therapy in the treatment of respiratory tract infections.

  11. Living situation affects adherence to combination antiretroviral therapy in HIV-infected adolescents in Rwanda: a qualitative study

    NARCIS (Netherlands)

    Mutwa, P.R.; Ilo van Nuil, J.; Asiimwe-Kateera, B.; Kestelyn, E.; Vyankandondera, J.; Pool, R.; Ruhirimbura, J.; Kanakuze, C.; Reiss, P.; Geleen, S.; van de Wijgert, J.; Boer, K.R.

    2013-01-01

    Introduction Adherence to combination antiretroviral therapy (cART) is vital for HIV-infected adolescents for survival and quality of life. However, this age group faces many challenges to remain adherent. We used multiple data sources (role-play, focus group discussions (FGD), and in-depth

  12. Triple combination antibiotic therapy for carbapenemase-producing Klebsiella pneumoniae: a systematic review.

    Science.gov (United States)

    Jacobs, David M; Safir, M Courtney; Huang, Dennis; Minhaj, Faisal; Parker, Adam; Rao, Gauri G

    2017-11-25

    The spread of carbapenemase-producing K. pneumoniae (CPKP) has become a significant problem worldwide. Combination therapy for CPKP is encouraging, but polymyxin resistance to many antibiotics is hampering effective treatment. Combination therapy with three or more antibiotics is being increasingly reported, therefore we performed a systematic review of triple combination cases in an effort to evaluate their clinical effectiveness for CPKP infections. The PubMed database was searched to identify all published clinical outcomes of CPKP infections treated with triple combination therapy. Articles were stratified into two tiers depending on the level of clinical detail provided. A tier 1 study included: antibiotic regimen, regimen-specific outcome, patient status at onset of infection, and source of infection. Articles not reaching these criteria were considered tier 2. Thirty-three studies were eligible, 23 tier 1 and ten tier 2. Among tier 1 studies, 53 cases were included in this analysis. The most common infection was pneumonia (31%) followed by primary or catheter-related bacteremia (21%) and urinary tract infection (17%). Different combinations of antibiotic classes were utilized in triple combinations, the most common being a polymyxin (colistin or polymyxin B, 86.8%), tigecycline (73.6%), aminoglycoside (43.4%), or carbapenem (43.4%). Clinical and microbiological failure occurred in 14/39 patients (35.9%) and 22/42 patients (52.4%), respectively. Overall mortality for patients treated with triple combination therapy was 35.8% (19/53 patients). Triple combination therapy is being considered as a treatment option for CPKP. Polymyxin-based therapy is the backbone antibiotic in these regimens, but its effectiveness needs establishing in prospective clinical trials.

  13. Living situation affects adherence to combination antiretroviral therapy in HIV-infected adolescents in Rwanda: a qualitative study

    NARCIS (Netherlands)

    Mutwa, Philippe R.; van Nuil, Jennifer Ilo; Asiimwe-Kateera, Brenda; Kestelyn, Evelyne; Vyankandondera, Joseph; Pool, Robert; Ruhirimbura, John; Kanakuze, Chantal; Reiss, Peter; Geelen, Sibyl; van de Wijgert, Janneke; Boer, Kimberly R.

    2013-01-01

    Adherence to combination antiretroviral therapy (cART) is vital for HIV-infected adolescents for survival and quality of life. However, this age group faces many challenges to remain adherent. We used multiple data sources (role-play, focus group discussions (FGD), and in-depth interviews (IDI)) to

  14. Osteoarticular infection caused by MDR Pseudomonas aeruginosa: the benefits of combination therapy with colistin plus β-lactams.

    Science.gov (United States)

    Ribera, Alba; Benavent, Eva; Lora-Tamayo, Jaime; Tubau, Fe; Pedrero, Salvador; Cabo, Xavier; Ariza, Javier; Murillo, Oscar

    2015-12-01

    In the era of emergence of MDR Pseudomonas aeruginosa, osteoarticular infections (OIs) add more difficulties to its treatment. The role of β-lactams (BLs) is questioned and older drugs need to be reconsidered. The objective of this study was to describe our experience in the management of OIs caused by MDR P. aeruginosa and evaluate different therapeutic options. This was a retrospective analysis of a prospectively collected cohort (2004-13) of patients with OI caused by MDR P. aeruginosa. We created two groups: (i) Group A (more difficult to treat), prosthetic joint infections (PJIs) and osteoarthritis (OA) managed with device retention; and (ii) Group B (less difficult to treat), OA managed without device retention. Antibiotic treatment was administered according to clinician criteria: monotherapy/combined therapy; and BL used by intermittent bolus (IB)/continuous infusion. Of 34 patients, 15 (44.1%) had PJI and 19 (55.9%) had OA (8 related to an orthopaedic device). Twenty-three cases (68%) were caused by XDR P. aeruginosa. The initial management included removal of an orthopaedic device in 14 cases, together with antibiotic [alone, 19 (55.9%; 4 colistin, 14 BL-IB and 1 BL continuous infusion); and in combination, 15 (44.1%; 5 BL-IB and 10 BL continuous infusion)]. The overall cure rate was 50% (39% and 63% in Groups A and B, respectively), ranging from 31.6% with monotherapy to 73.3% with combined therapy (P = 0.016), with special interest within Group A (cure rate with combined therapy 71.4%, P = 0.049). After rescue therapy, which included removal of remaining devices, the cure rate reached 85.3%. We suggest that the BL/colistin combination is an optimized therapy for OI caused by MDR P. aeruginosa, together with an appropriate surgical treatment. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. Efficacy of Fluoroquinolone/Probiotic Combination Therapy for Recurrent Urinary Tract Infection in Children: A Retrospective Analysis.

    Science.gov (United States)

    Madden-Fuentes, Ramiro J; Arshad, Mehreen; Ross, Sherry S; Seed, Patrick C

    2015-09-01

    Children with normal urinary tract anatomy and function and highly recurrent urinary tract infection (rUTI) may have a lack of alternatives when antibiotic prophylaxis and "watchful waiting" approaches fail. This retrospective review reports the outcomes in children who received a fluoroquinolone/probiotic combination in an attempt to quantify a reduction in rUTI that was perceived by both clinicians and patients' families. Data from all children with rUTIs previously managed with a fluoroquinolone/probiotic combination at the Pediatric Infectious Diseases Clinic at Duke University Medical Center (Durham, North Carolina) were identified and analyzed. Data from 10 children were eligible for inclusion. Compared with before therapy initiation, total UTI episodes were significantly fewer after therapy initiation (57 vs 4; P = 0.0001). Seven (70%) were free of rUTIs during the follow-up period. Of the 8 patients with known compliance, 7 (88%) were free of rUTIs. Given the chronic nature of these patients' symptoms, the significant decrease in UTI after the initiation of therapy, and the increase in the interval without an infection and/or its symptoms, this treatment regimen has the potential to improve overall quality of life, decrease antibiotic courses, and decrease health care costs in children with rUTI. These results will be validated with a larger cohort of patients in a prospective, randomized trial. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

  16. [To the issue of local treatment in combination therapy of chronic urethritis, associated with sexually transmitted infections].

    Science.gov (United States)

    Abdrahmanov, R M; Fajzullina, E V; Abdrahmanov, A R; Haliullin, R R

    2015-12-01

    The article shows the high efficacy of the additional local use of the drug Miramistin in combination therapy of chronic urethritis, associated with sexually transmitted infections (STIs). In accordance with the principles of evidence-based medicine, patients were assigned to the study group (n=110) treated with conventional therapy and Miramistin, and the comparison group (n=40) treated with conventional therapy only. The between-group comparison of treatment effectiveness was carried out by matching results of the etiological healing, the changes of the endoscopic picture of the urethra, and basic clinical manifestations of STI: the degree of inflammatory reaction of urethral mucous membrane, dysuria, pain and sexual syndrome.

  17. [Combination therapy of chronic bacterial prostatitis].

    Science.gov (United States)

    Khryanin, A A; Reshetnikov, O V

    2016-08-01

    The article discusses the possible etiological factors in the development of chronic bacterial prostatitis. The authors presented a comparative long-term analysis of morbidity from non-viral sexually transmitted infections (STIs) in Russia. Against the background of general decline in STIs incidence, a significant percentage of them is made up by urogenital trichomoniasis. The findings substantiated the advantages of combination therapy (ornidazole and ofloxacin) for bacterial urinary tract infections.

  18. [Herpetic infection in patients with psoriasis: the improvement of therapy].

    Science.gov (United States)

    Shul'diakov, A A; Barkhatova, T S; Satarova, S A; Perminova, T A

    2012-01-01

    The aim of the study was to estimate the efficacy of liniment cycloferon included in combined therapy of herpetic infection in 30 patients with psoriasis divided into 2 groups. Combined treatment of patients with recurrent herpetic infection promoted elimination of general infection syndrome, shortened duration of eruption and local inflammation, accelerated epithelization of herpetic erosion, and decreased the frequency of relapses during the follow-up.

  19. FIRST EXPERIENCE OF CYMEVEN IN THE COMBINED THERAPY OF RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    R M Balabanova

    2001-01-01

    Full Text Available Ummary Objective. To reveal J'reguency of accompaning virus infection and possibility to use antivirus therapy together in therapy RA. Material. 40 patients with RA at the age of 17-45 were studied. The duration of disease was not more than 6 months; patients had 2-3 degrees of activity. Every one had a positive rheumatoid factor. Results. 78,2% of the examined patients connected the beginning of the illness with virus infection they have had. The most difficalt variant of RA course and uneffectiveness of basic therapy were registerd among the patients with combination HSV and CMV infection. Inclusion of Cymevene in complex therapy RA has exerted positive influence on clinical-laboratory, signs stregthened effect of basic therapy. Conclusion. The most difficult variant of RA course was registered among the patients with virus infection. Inclusion of antivirus drugs had a positive influence on effectiveness of basic therapy.

  20. Combined Therapy at Persistent Herpes Virus Infection in Sickly Children

    Directory of Open Access Journals (Sweden)

    F. S. Kharlamova

    2012-01-01

    Full Text Available We examined 40 sickly children with recurrent croup (RC — 28 and bronchial obstruction (ROB — 8, (RC + ROB — 4 aged from 18 months till 14 years. We found that high frequency of persistent herpes viruses usually occurs as associations with CMV, EBV and human herpes virus 6 type. We substantiated anti viral and immune corrective therapy in two schemes compared in efficacy: the 1st group was administered monotherapy with Viferon, and the 2nd group received combined therapy Viferon + Arbidol in doses according to the age during three months. We received a more expressed clinical immunologic effect from the therapy with decreased antigenic load and frequency of recurrence of RC and ROB with Viferon application in suppositories in combination with Arbidol per orally in the intermittent scheme during three months. 

  1. Perinatal HIV-infection in Sankt Petersburg and Modern Therapy Concomitant Viral Infections

    Directory of Open Access Journals (Sweden)

    V. N. Timchenko

    2016-01-01

    Full Text Available The study included 338 HIV-infected children (B-23 and 350 children with perinatal contact HIV infection (R-75, consisting on the dispensary in the department of maternal and child the St. Petersburg City AIDS Center. In 32 persons (9.5% diagnosed with secondary infections. In the structure of viral opportunistic infections (herpesvirus, SARS amounted to 39.8%, bacterial (bronchitis, tonsillitis, pyoderma, tuberculosis — 34.8%, fungal and parasitic (candidiasis of the oral mucosa, PCP — 25.4 %. Combined therapy (causal, pathogenetic, symptomatic SARS in children with B-23 and R-75, allows you to get in early (6th d. Treatment regress the main symptoms of acute respiratory diseases. Modern therapy of congenital cytomegalovirus infection (VTSMI in children with B-23 and R-75 of the first year of life with antitsitomegalovirusnogo immunoglobulin and preparation of human recombinant interferon alfa-2b in the form of rectal suppositories — VIFERON, causes persistent normalization of clinical and laboratory parameters.

  2. Efficacy of combined antiviral therapy with pegylated interferon α-2a and ribavirin for chronic hepatitis C infection in intravenous drug users

    Directory of Open Access Journals (Sweden)

    Ružić Maja

    2010-01-01

    Full Text Available Introduction. Hepatitis C Virus infection represents not just a medical, but also a socio-economic problem. It is estimated that among 170 million infected, 60% belongs to the category of intravenous drug users (IDUs. Objective. The aim of this paper was to compare the response to the combined therapy of pegylated interferon alfa 2a and ribavirin, in the group of patients with HCV infection who were intravenous drug users (IDUs and in patients who were identified in the other way of transmission of HCV. Also to identify the influence of the therapy on diseases of addiction, during the course of HCV infection and on the effects of the combined therapy of pegylated interferon alfa 2a and ribavirin. Methods. We conducted a retrospective-prospective study, on 60 patients, treated with combined antiviral therapy-pegylated interferon alfa 2a and ribavirin. 30 patients were from the group of IDUs, and 30 patients from other epidemiological groups. Results. There were significant differences between the age of the patients (30.2±7.1 vs. 39.3±11.2 years; p=0.002, but no significant difference in the duration of the HCV infection between the two groups of patients (8.9±7.4 vs. 13.1±7.0 years; p>0.05. A large number of the patients in the group of IDUs had a problem with the abstinence of the drug abuse. In this group, there was the influence of alcohol (30% and other substances with potential hepatotoxicity: marihuana (23.3% and psycho-active drugs (73.6%. Staging of the liver fibrosis was not influenced by those two parameters and was similar in both groups (p>0.05. The genotype 3a was dominant in intravenous drug users (50.0% and genotype 1b in the control group of the patients (76.6%. In both groups, SVR was achieved at a higher percentage (86% vs. 70.00%; p>0.05, but among the intravenous drug users the relapses of HCV infection were at a lower percentage (3.3% vs. 20.0%; p=0.044. Side effects were noticed in solitary cases in both of the examined

  3. Factors contributing to risk for cancer among HIV-infected individuals, and evidence that earlier combination antiretroviral therapy will alter this risk

    DEFF Research Database (Denmark)

    Borges, Alvaro Humberto Diniz; Dubrow, Robert; Silverberg, Michael J

    2014-01-01

    PURPOSE OF REVIEW: To critically appraise recent published literature about factors associated with cancer risk likely to be influenced by combination antiretroviral therapy (cART) in HIV-infected individuals, and the potential of earlier cART initiation to reduce this risk. RECENT FINDINGS: Fact...

  4. [Clinical effect of triple therapy combined with Saccharomyces boulardii in the treatment of Helicobacter pylori infection in children].

    Science.gov (United States)

    Zhao, Hong-Mei; Ou-Yang, Hong-Juan; Duan, Bo-Ping; Xu, Bin; Chen, Zhi-Yong; Tang, Juan; You, Jie-Yu

    2014-03-01

    To evaluate the clinical effect of proton pump inhibitor-based triple therapy combined with Saccharomyces boulardii in the treatment of Helicobacter pylori (Hp) infection among children in terms of Hp eradication rate and incidence of adverse events. A prospective randomised controlled study was conducted on 240 children with a confirmed diagnosis of Hp infection. These patients were randomized into triple therapy (n=120) and probiotics groups (n=120). The triple therapy group received amoxicillin [40 mg/(kg·d), Tid], clarithromycin [15 mg/(kg·d), Bid] and omeprazole [0.7-0.8 mg/(kg·d), Qd], while the probiotics group received Saccharomyces boulardii (250 mg, Bid) in addition to triple therapy. The course of treatment was 14 days in both groups. The adverse events in subjects were recorded by their parents during treatment. Hp eradiation was evaluated by (13)C breath test at 4 weeks after treatment, and the eradication rate and incidence of adverse events were compared between the two groups. The Hp eradication rates were 75.8% (91/120) in the triple therapy group and 85% (102/120) in the probiotics group (P>0.05). Compared with the triple therapy group, the probiotics group had nonsignificantly lower incidence of nausea, vomiting, and abdominal pain (P>0.05) and significantly lower incidence of stomatitis, constipation and diarrhea (PSaccharomyces boulardii cannot significantly increase Hp eradication rate, but can significantly reduce the incidence of stomatitis, constipation, and diarrhea during treatment.

  5. The effect of combined drugs therapy on the course of clinical rabies infection in a murine model.

    Science.gov (United States)

    Smreczak, Marcin; Orłowska, Anna; Marzec, Anna; Trębas, Paweł; Kycko, Anna; Reichert, Michał; Koraka, Penelope; Osterhaus, Albert D M E; Żmudziński, Jan Franciszek

    2018-04-09

    Rabies is a fatal disease of all mammals causing almost 60,000 human deaths every year. To date, there is no effective treatment of clinical rabies once the symptoms appear. Here, we describe the promising effect of combination therapy composed of molecules that target replication of the rabies virus (RV) at different stages of life cycle and molecules that inhibit some pathways of the innate host immune response accompanied by a blood-brain barrier opener on the outcome of RV infection. The study reports statistically significant extension of survival of mice treated with the drug cocktail containing T-705, ribavirin, interferon α/β, caspase-1 inhibitor, TNF-α inhibitor, MAPKs inhibitor and HRIG compared to the survival of mice in the virus control group (p = 0.0312). Furthermore, the study points to the significant impact of interferon α/β on the survival of RV-infected mice. We have shown a significant down regulation of pro-inflammatory molecules (caspase-1 and TNF-a) in the CNS in RV-infected mice treated with a combination of drugs including interferon α/β. Copyright © 2018. Published by Elsevier Ltd.

  6. Early diagnosis and empiric therapy for cirrhosis associated with infection

    Directory of Open Access Journals (Sweden)

    NAN Yuemin

    2015-03-01

    Full Text Available Infection is a frequent complication of cirrhosis, which often occurs in the lungs, chest, abdomen, biliary tract, urinary tract, soft tissue, and skin, and occasionally causes spontaneous bacteremia in patients. This paper reviews the risk factors and common types of infection in cirrhosis associated with infection, and the early diagnosis and symptomatic treatment of different types of infection. Moreover, this paper points out that cirrhosis associated with infection is a key factor for disease progression and the early diagnosis and treatment are essential for successful treatment. The third-generation cephalosporins are the first-line antibiotic agents. Drug-resistant bacteria should be treated with antibiotic compound containing β-lactamase inhibitors or carbapenems. Methicillin-resistant Staphylococcus aureus should be treated with glycopeptide antibiotics or combination therapies. Pulmonary mycoses are mainly treated with caspofungin or voriconazole. Antibiotics combined with supportive therapies including the administration of albumin can improve the treatment outcome and prognosis.

  7. Maternal Nutritional Status Predicts Adverse Birth Outcomes among HIV-Infected Rural Ugandan Women Receiving Combination Antiretroviral Therapy

    Science.gov (United States)

    Young, Sera; Murray, Katherine; Mwesigwa, Julia; Natureeba, Paul; Osterbauer, Beth; Achan, Jane; Arinaitwe, Emmanuel; Clark, Tamara; Ades, Veronica; Plenty, Albert; Charlebois, Edwin; Ruel, Theodore; Kamya, Moses; Havlir, Diane; Cohan, Deborah

    2012-01-01

    Objective Maternal nutritional status is an important predictor of birth outcomes, yet little is known about the nutritional status of HIV-infected pregnant women treated with combination antiretroviral therapy (cART). We therefore examined the relationship between maternal BMI at study enrollment, gestational weight gain (GWG), and hemoglobin concentration (Hb) among 166 women initiating cART in rural Uganda. Design Prospective cohort. Methods HIV-infected, ART-naïve pregnant women were enrolled between 12 and 28 weeks gestation and treated with a protease inhibitor or non-nucleoside reverse transcriptase inhibitor-based combination regimen. Nutritional status was assessed monthly. Neonatal anthropometry was examined at birth. Outcomes were evaluated using multivariate analysis. Results Mean GWG was 0.17 kg/week, 14.6% of women experienced weight loss during pregnancy, and 44.9% were anemic. Adverse fetal outcomes included low birth weight (LBW) (19.6%), preterm delivery (17.7%), fetal death (3.9%), stunting (21.1%), small-for-gestational age (15.1%), and head-sparing growth restriction (26%). No infants were HIV-infected. Gaining pregnancy, grossly inadequate GWG was common. Infants whose mothers gained <0.1 kg/week were at increased risk for LBW, preterm delivery, and composite adverse birth outcomes. cART by itself may not be sufficient for decreasing the burden of adverse birth outcomes among HIV-infected women. Trial Registration Clinicaltrials.gov NCT00993031 PMID:22879899

  8. Persisting Inflammation and Chronic Immune Activation but Intact Cognitive Function in HIV-Infected Patients After Long-Term Treatment With Combination Antiretroviral Therapy

    DEFF Research Database (Denmark)

    Pedersen, Karin K; Pedersen, Maria; Gaardbo, Julie C

    2013-01-01

    Impaired cognitive function in HIV-infected patients has been suggested. Treatment with combination antiretroviral therapy (cART) restores CD4⁺ cell counts and suppresses viral replication, but immune activation and inflammation may persist. The aim of the study was to examine if cognitive function...

  9. Combination Antifungal Therapy in the Treatment of Scedosporium apiospermum Central Nervous System Infections

    Directory of Open Access Journals (Sweden)

    Andrés F. Henao-Martínez

    2013-01-01

    Full Text Available Treatment of Scedosporium apiospermum central nervous system (CNS infection typically consists of an azole in combination with surgical debridement. This approach requires prolonged treatment and carries a high associated mortality. We present two cases of the successful treatment of S. apiospermum CNS infections with the combination of voriconazole and terbinafine.

  10. Efficacy of antibiotic treatment of implant-associated Staphylococcus aureus infections with moxifloxacin, flucloxacillin, rifampin, and combination therapy: an animal study.

    Science.gov (United States)

    Greimel, Felix; Scheuerer, Christine; Gessner, Andre; Simon, Michaela; Kalteis, Thomas; Grifka, Joachim; Benditz, Achim; Springorum, Hans-Robert; Schaumburger, Jens

    2017-01-01

    The efficacy of antibiotic monotherapy and combination therapy in the treatment of implant-associated infection by Staphylococcus aureus was evaluated in an animal study. The femoral medullary cavity of 66 male Wistar rats was contaminated with S. aureus (ATCC 29213) and a metal device was implanted, of which 61 could be evaluated. Six treatment groups were studied: flucloxacillin, flucloxacillin in combination with rifampin, moxifloxacin, moxifloxacin in combination with rifampin, rifampin, and a control group with aqua. The treatment was applied for 14 days. After euthanasia, the bacterial counts in the periprosthetic bone, the soft tissue, and the implant-associated biofilm were measured. Both antibiotic combination treatments (moxifloxacin plus rifampin and flucloxacillin plus rifampin) achieved a highly significant decrease in microbial counts in the bone and soft tissue and in the biofilm. Mono-antibiotic treatments with either moxifloxacin or flucloxacillin were unable to achieve a significant decrease in microbial counts in bone and soft tissue or the biofilm, whilst rifampin was able to reduce the counts significantly only in the biofilm. Antibiotic resistance was measured in 1/3 of the cases in the rifampin group, whereas no resistance was measured in all other groups. The results show that combinations of both moxifloxacin and flucloxacillin plus rifampin are adequate for the treatment of periprosthetic infections due to infections with S. aureus , whereas monotherapies are not effective or not applicable due to the rapid development of antibiotic resistance. Therefore, moxifloxacin is an effective alternative in combination with rifampin for the treatment of implant-associated infections.

  11. Dual antiretroviral therapy for HIV infection.

    Science.gov (United States)

    Soriano, Vicente; Fernandez-Montero, Jose Vicente; Benitez-Gutierrez, Laura; Mendoza, Carmen de; Arias, Ana; Barreiro, Pablo; Peña, José M; Labarga, Pablo

    2017-08-01

    For two decades, triple combinations of antiretrovirals have been the standard treatment for HIV infection. The challenges of such lifelong therapy include long-term side effects, high costs and reduced drug adherence. The recent advent of more potent and safer antiretrovirals has renewed the interest for simpler HIV regimens. Areas covered: We discuss the pros and cons of dual antiretroviral therapies in both drug-naïve and in treatment-experienced patients with viral suppression (switch strategy). Expert opinion: Some dual antiretroviral regimens are safe and efficacious, particularly as maintenance therapy. At this time, combinations of dolutegravir plus rilpivirine represent the best dual regimen. Longer follow-up and larger study populations are needed before supporting dolutegravir plus lamivudine. In contrast, dual therapy based on maraviroc is less effective. Although dual regimens with boosted protease inhibitors plus either lamivudine or raltegravir may be effective, they are penalized by metabolic side effects and risk for drug interactions. The newest dual regimens could save money, reduce toxicity and spare drug options for the future. For the first time in HIV therapeutics, less can be more. Dual therapy switching has set up a new paradigm in HIV treatment that uses induction-maintenance.

  12. Sofosbuvir and Simeprevir Combination Therapy for HCV Genotype 1 Infection: Results of a Single-Center VA Experience

    Science.gov (United States)

    Hernandez, Maria Del Pilar; Vance, Evan; Gilinski, Dani; Youtseff, Helen; Toro, Maribel; Antoine, Marie; Jeffers, Lennox J.; Peyton, Adam

    2016-01-01

    Treatment of chronic hepatitis C virus (HCV) infection remains a priority in the veterans affairs (VA) health care system nationwide, as there is a high burden of liver disease due to HCV infection among US veterans. The combination of sofosbuvir and simeprevir was the first all-oral antiviral regimen used in clinical practice to treat veterans with HCV infection. In this study, we report a single-center experience showing both the feasibility and effectiveness of this all-oral combination to treat HCV genotype 1 infection. One hundred patients with HCV genotype 1 infection were treated between December 2013 and June 2014. Eighty-six patients were treated with sofosbuvir and simeprevir, with or without ribavirin, for 12 weeks; 12 patients were treated with sofosbuvir, pegylated interferon, and ribavirin for 12 weeks; and 2 patients were treated with sofosbuvir and ribavirin for 24 weeks. Overall, treatment was well tolerated and feasible, with compliance rates over 95% in patients treated with all-oral therapy. The sustained virologic response (SVR) rate for sofosbuvir and simeprevir (88.4%) was superior to the rate for sofosbuvir, pegylated interferon, and ribavirin (50.0%). Subgroup analysis showed diminished SVR rates in cirrhotic patients vs noncirrhotic patients. There were no significant differences in SVR when comparing treatment with or without ribavirin or among genotype subtypes. In conclusion, this study demonstrated excellent completion rates for all-oral treatment of veterans with chronic HCV infection. Additionally, treatment was highly effective, nearing a 90% cure rate. Thus, we recommend that the VA health care system continue to incorporate new HCV medications into its formulary so as to expand HCV treatment for US veterans. PMID:27917084

  13. Add-On Therapy with Ertapenem in Infections with Multidrug Resistant Gram-Negative Bacteria: Pediatric Experience

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    Sevgen Tanır Basaranoglu

    2017-01-01

    Full Text Available Optimal therapy for infections with carbapenem resistant GNB is not well established due to the weakness of data. Patients presenting with bloodstream infections caused by multidrug resistant Klebsiella pneumoniae were treated with a combination treatment. Optimal therapy for infections with carbapenem resistant Gram-negative bacteria is a serious problem in pediatric patients. We presented three cases who were successfully treated with addition of ertapenem to the combination treatment for bacteremia with multidrug resistant Klebsiella pneumoniae. Dual carbapenem treatment approach is a new approach for these infections and requires more data in children.

  14. Immediate Antiretroviral Therapy Reduces Risk of Infection-Related Cancer During Early HIV Infection

    DEFF Research Database (Denmark)

    Borges, Alvaro Humberto Diniz; Neuhaus, Jacqueline; Babiker, Abdel G

    2016-01-01

    BACKGROUND:  In the Strategic Timing of Antiretroviral Treatment (START) study, immediate combination antiretroviral therapy (cART) initiation reduced cancer risk by 64%. We hypothesized that risk reduction was higher for infection-related cancer and determined by differences in CD4 cell counts a...

  15. Efficacy of antibiotic treatment of implant-associated Staphylococcus aureus infections with moxifloxacin, flucloxacillin, rifampin, and combination therapy: an animal study

    Directory of Open Access Journals (Sweden)

    Greimel F

    2017-06-01

    Full Text Available Felix Greimel,1 Christine Scheuerer,1 Andre Gessner,2 Michaela Simon,2 Thomas Kalteis,1 Joachim Grifka,1 Achim Benditz,1 Hans-Robert Springorum,1 Jens Schaumburger1 1Department of Orthopedics, University Medical Center Regensburg, Asklepios Klinikum Bad Abbach, Bad Abbach, 2Institute of Clinical Microbiology and Hygiene, University Medical Center Regensburg, Regensburg, Bavaria, Germany Abstract: The efficacy of antibiotic monotherapy and combination therapy in the treatment of implant-associated infection by Staphylococcus aureus was evaluated in an animal study. The femoral medullary cavity of 66 male Wistar rats was contaminated with S. aureus (ATCC 29213 and a metal device was implanted, of which 61 could be evaluated. Six treatment groups were studied: flucloxacillin, flucloxacillin in combination with rifampin, moxifloxacin, moxifloxacin in combination with rifampin, rifampin, and a control group with aqua. The treatment was applied for 14 days. After euthanasia, the bacterial counts in the periprosthetic bone, the soft tissue, and the implant-associated biofilm were measured. Both antibiotic combination treatments (moxifloxacin plus rifampin and flucloxacillin plus rifampin achieved a highly significant decrease in microbial counts in the bone and soft tissue and in the biofilm. Mono-antibiotic treatments with either moxifloxacin or flucloxacillin were unable to achieve a significant decrease in microbial counts in bone and soft tissue or the biofilm, whilst rifampin was able to reduce the counts significantly only in the biofilm. Antibiotic resistance was measured in 1/3 of the cases in the rifampin group, whereas no resistance was measured in all other groups. The results show that combinations of both moxifloxacin and flucloxacillin plus rifampin are adequate for the treatment of periprosthetic infections due to infections with S. aureus, whereas monotherapies are not effective or not applicable due to the rapid development of

  16. Maternal nutritional status predicts adverse birth outcomes among HIV-infected rural Ugandan women receiving combination antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Sera Young

    Full Text Available Maternal nutritional status is an important predictor of birth outcomes, yet little is known about the nutritional status of HIV-infected pregnant women treated with combination antiretroviral therapy (cART. We therefore examined the relationship between maternal BMI at study enrollment, gestational weight gain (GWG, and hemoglobin concentration (Hb among 166 women initiating cART in rural Uganda.Prospective cohort.HIV-infected, ART-naïve pregnant women were enrolled between 12 and 28 weeks gestation and treated with a protease inhibitor or non-nucleoside reverse transcriptase inhibitor-based combination regimen. Nutritional status was assessed monthly. Neonatal anthropometry was examined at birth. Outcomes were evaluated using multivariate analysis.Mean GWG was 0.17 kg/week, 14.6% of women experienced weight loss during pregnancy, and 44.9% were anemic. Adverse fetal outcomes included low birth weight (LBW (19.6%, preterm delivery (17.7%, fetal death (3.9%, stunting (21.1%, small-for-gestational age (15.1%, and head-sparing growth restriction (26%. No infants were HIV-infected. Gaining <0.1 kg/week was associated with LBW, preterm delivery, and a composite adverse obstetric/fetal outcome. Maternal weight at 7 months gestation predicted LBW. For each g/dL higher mean Hb, the odds of small-for-gestational age decreased by 52%.In our cohort of HIV-infected women initiating cART during pregnancy, grossly inadequate GWG was common. Infants whose mothers gained <0.1 kg/week were at increased risk for LBW, preterm delivery, and composite adverse birth outcomes. cART by itself may not be sufficient for decreasing the burden of adverse birth outcomes among HIV-infected women.Clinicaltrials.gov NCT00993031.

  17. Efficacy in Treatment of Cervical HrHPV Infection by Combination of Beta Interferon, and Herbal Therapy in Woman with Different Cervical Lesions

    Directory of Open Access Journals (Sweden)

    Ermina Iljazović

    2008-11-01

    therapy. The almost same therapy was recommended to the male partner. Patients from the second group used B complex during the therapy. Patients were retested for the HPV presence after three or six month from therapy depend of the presence bacterial or fungal genital coinfection. Three months after applied therapy HPV infection was still present in more than 90% of the patients in the first group. In the second group treated according to the recommended therapy scheme HPV infection disappeared in 71.42% of the patients after three months and in 100% of patients after six months. Samples of the cervical smear for the HPV analysis were being taken during routine gynecological examinations, by using sticks with cotton, taken from the Digene Specimen Collection Kit, from the whole surface of a portion, and by mild rotating moves from the outer cervical entrance. Our results suggest that the combination of interferon and herbal therapy with B complex is effective, atraumatic and simple non-surgical treatment of HPV infection. Since prospective efficacy trials will take several years to complete, considering alternative approaches is also worthwhile.

  18. [Improvement of parodontitis therapy of patients with HIV-infection].

    Science.gov (United States)

    Soboleva, L A; Oseeva, A O; Shul'diakov, A A; Bulkina, N V

    2010-01-01

    For the purpose to determine the clinic-pathogenetic efficacy of cycloferon liniment in the combined therapy of periodontitis of patients with subclinical stage of HIV-infection medical examination and treatment of 40 patients was carried out. It was established that use of liniment cycloferon in the combined treatment of patients with subclinical stage of HIV-infection allowed to accelerate process of normalization of lipid peroxidation parameters and antioxidant potential of blood, to decrease infection load (herpes symplex virus I, Candida albicans, Staphylococcus aureus) in parodontal recess and evidence of local inflammation with reduction of activity of the tumours necrosis factor and interleukin 1beta, what provided acceleration of recuperation processes, lowering the frequency of parodontitis relapses.

  19. Evaluation of combination therapy for Burkholderia cenocepacia lung infection in different in vitro and in vivo models.

    Directory of Open Access Journals (Sweden)

    Freija Van den Driessche

    Full Text Available Burkholderia cenocepacia is an opportunistic pathogen responsible for life-threatening infections in cystic fibrosis patients. B. cenocepacia is extremely resistant towards antibiotics and therapy is complicated by its ability to form biofilms. We investigated the efficacy of an alternative antimicrobial strategy for B. cenocepacia lung infections using in vitro and in vivo models. A screening of the NIH Clinical Collection 1&2 was performed against B. cenocepacia biofilms formed in 96-well microtiter plates in the presence of tobramycin to identify repurposing candidates with potentiator activity. The efficacy of selected hits was evaluated in a three-dimensional (3D organotypic human lung epithelial cell culture model. The in vivo effect was evaluated in the invertebrate Galleria mellonella and in a murine B. cenocepacia lung infection model. The screening resulted in 60 hits that potentiated the activity of tobramycin against B. cenocepacia biofilms, including four imidazoles of which econazole and miconazole were selected for further investigation. However, a potentiator effect was not observed in the 3D organotypic human lung epithelial cell culture model. Combination treatment was also not able to increase survival of infected G. mellonella. Also in mice, there was no added value for the combination treatment. Although potentiators of tobramycin with activity against biofilms of B. cenocepacia were identified in a repurposing screen, the in vitro activity could not be confirmed nor in a more sophisticated in vitro model, neither in vivo. This stresses the importance of validating hits resulting from in vitro studies in physiologically relevant model systems.

  20. Anti-inflammatory therapy for urinary tract infection in children

    Directory of Open Access Journals (Sweden)

    A. A. Vyalkova

    2015-01-01

    Full Text Available Objective: to substantiate the importance of an etiological approach to diagnosing urinary tract infection in children in terms of the species and biological properties of an infectious agent and to evaluate the efficiency of anti-inflammatory therapy. The study included 116 patients aged 3-15 years with chronic pyelonephritis (Group 1 and isolated bacteriuria (Group 2. After 10-14-day antibiotic therapy, Group 1 patients were allocated to two subgroups: Subgroup la («=30 took furamag 5 mg/kg/day; Subgroup lb («=30 received furamag at the same dose in combination with canephron. The treatment cycle lasted 10-14 days. Subgroup 2a («=26 children had furamag 5 mgДg/day and Subgroup 2b (« =30 took furamag in combination with canephron. The duration of treatment was 14 days. The investigators established the high efficiency of therapy with furamag for renal infection in the children with the active and decrement phases and that of the drug of choice for its monotherapy of isolated highly virulent bacteriuria. Therapeutic efficiency was proven to be related to the species and biological characteristics of an infectious agent. Anti-inflammatory therapy for pyelonephritis in terms of the species of pathogenic bacteria was ascertained to improve the efficiency of treatment. A rationale was provided for the individual choice of antibiotics, followed by the use of furamag, eubiotics, and drugs aimed at inhibiting virulence factors and persistence of the pathogen to sanitize the primary focus of infection.

  1. Early use of negative pressure therapy in combination with silver dressings in a difficult breast abscess.

    Science.gov (United States)

    Richards, Alastair J; Hagelstein, Sue M; Patel, Girish K; Ivins, Nicola M; Sweetland, Helen M; Harding, Keith G

    2011-12-01

    Combining silver-based dressings with negative pressure therapy after radical excision of chronically infected breast disease is a novel application of two technologies. One patient with complex, chronic, infected breast disease underwent radical excision of the affected area and was treated early with a combination of silver-based dressings and topical negative pressure therapy. The wound was then assessed sequentially using clinical measurements of wound area and depth, pain severity scores and level of exudation. It is possible to combine accepted techniques with modern dressing technologies that result in a positive outcome. In this case, the combination of a silver-based dressing with negative pressure therapy following radical excision proved safe and was well tolerated by the patient. Full epithelisation of the wound was achieved and there was no recurrence of the infection for the duration of the treatment. © 2011 The Authors. © 2011 Blackwell Publishing Ltd and Medicalhelplines.com Inc.

  2. Outcome of E1224-Benznidazole Combination Treatment for Infection with a Multidrug-Resistant Trypanosoma cruzi Strain in Mice.

    Science.gov (United States)

    Diniz, Lívia de Figueiredo; Mazzeti, Ana Lia; Caldas, Ivo Santana; Ribeiro, Isabela; Bahia, Maria Terezinha

    2018-06-01

    Combination therapy has been proposed as an alternative therapeutic approach for the treatment of Chagas disease. In this study, we evaluated the effect of treatment with benznidazole combined with E1224 (ravuconazole prodrug) in an experimental murine model of acute infection. The first set of experiments assessed the range of E1224 doses required to induce parasitological cure using Trypanosoma cruzi strains with different susceptibilities to benznidazole (Y and Colombian). All E1224 doses were effective in suppressing the parasitemia and preventing death; however, parasitological cure was observed only in mice infected with Y strain. Considering these results, we evaluated the effect of combined treatment against Colombian, a multidrug-resistant T. cruzi strain. After exclusion of antagonistic effects using in vitro assays, infected mice were treated with E1224 and benznidazole in monotherapy or in combination at day 4 or 10 postinoculation. All treatments were well tolerated and effective in suppressing parasitemia; however, parasitological and PCR assays indicated no cure among mice treated with monotherapies. Intriguingly, the outcome of combination therapy was dependent on treatment onset. Early treatment using optimal doses of E1224-benznidazole induced a 100% cure rate, but this association could not eliminate a well-established infection. The beneficial effect of combination therapy was evidenced by further reductions of the patent parasitemia period in the group receiving combined therapy compared with monotherapies. Our results demonstrated a positive interaction between E1224 and benznidazole against murine T. cruzi infection using a multidrug-resistant strain and highlighted the importance of a stringent experimental model in the evaluation of new therapies. Copyright © 2018 Diniz et al.

  3. IP-10 predicts the first phase decline of HCV RNA and overall viral response to therapy in patients co-infected with chronic hepatitis C virus infection and HIV

    DEFF Research Database (Denmark)

    Falconer, Karolin; Askarieh, Galia; Weis, Nina Margrethe

    2010-01-01

    The aim of this study was to investigate the utility of baseline plasma interferon-gamma inducible protein-10 (IP-10) levels in human immunodeficiency virus (HIV)-hepatitis C virus (HCV) co-infected patients. Baseline IP-10 was monitored during HCV combination therapy in 21 HIV-HCV co-infected pa......The aim of this study was to investigate the utility of baseline plasma interferon-gamma inducible protein-10 (IP-10) levels in human immunodeficiency virus (HIV)-hepatitis C virus (HCV) co-infected patients. Baseline IP-10 was monitored during HCV combination therapy in 21 HIV-HCV co......-10 viral response to HCV therapy in HIV-HCV co-infected patients, and may thus be useful in encouraging such difficult-to-treat patients to initiate therapy....

  4. When to initiate combined antiretroviral therapy to reduce mortality and AIDS-defining illness in HIV-infected persons in developed countries: an observational study

    NARCIS (Netherlands)

    Cain, Lauren E.; Logan, Roger; Robins, James M.; Sterne, Jonathan A. C.; Sabin, Caroline; Bansi, Loveleen; Justice, Amy; Goulet, Joseph; van Sighem, Ard; de Wolf, Frank; Bucher, Heiner C.; von Wyl, Viktor; Esteve, Anna; Casabona, Jordi; del Amo, Julia; Moreno, Santiago; Seng, Remonie; Meyer, Laurence; Perez-Hoyos, Santiago; Muga, Roberto; Lodi, Sara; Lanoy, Emilie; Costagliola, Dominique; Hernan, Miguel A.; Ainsworth, J.; Anderson, J.; Babiker, A.; Delpech, V.; Dunn, D.; Easterbrook, P.; Fisher, M.; Gazzard, B.; Gilson, R.; Gompels, M.; Hill, T.; Johnson, M.; Leen, C.; Orkin, C.; Phillips, A.; Pillay, D.; Porter, K.; Sabin, C.; Schwenk, A.; Walsh, J.; Bansi, L.; Glabay, A.; Thomas, R.; Jones, K.; Perry, N.; Pullin, A.; Churchill, D.; Nelson, M.; Asboe, D.; Bulbeck, S.; Mandalia, S.; Clarke, J.; Munshi, S.; Post, F.; Khan, Y.; Patel, P.; Karim, F.; Duffell, S.; Man, S. L.; Williams, I.; Dooley, D.; Youle, M.; Lampe, F.; Smith, C.; Grabowska, H.; Chaloner, C.; Ismajani Puradiredja, D.; Weber, J.; Kemble, C.; Mackie, N.; Winston, A.; Wilson, A.; Bezemer, D. O.; Gras, L. A. J.; Kesselring, A. M.; van Sighem, A. I.; Smit, C.; Zhang, S.; Zaheri, S.; Prins, J. M.; Boer, K.; Bos, J. C.; Geerlings, S. E.; Godfried, M. H.; Haverkort, M. E.; Kuijpers, T. W.; Lange, J. M. A.; van der Meer, J. T. M.; Nellen, F. J. B.; Pajkrt, D.; van der Poll, T.; Reiss, P.; Scherpbier, H. J.; van der Valk, M.; Vrouenraets, S. M. E.; van Vugt, M.; Wit, F. W. M. N.; Schreij, G.; Lowe, S.; Oude Lashof, A.; Bravenboer, B.; Pronk, M. J. H.; van der Ende, M. E.; van der Feltz, M.; Gelinck, L. B. S.; Nouwen, J. L.; Rijnders, B. J. A.; de Ruiter, E. D.; Slobbe, L.; Schurink, C. A. M.; Verbon, A.; de Vries-Sluijs, T. E. M. S.; Driessen, G.; Hartwig, N. G.; Branger, J.; Kauffmann, R. H.; Schippers, E. F.; Groeneveld, P. H. P.; Alleman, M. A.; Bouwhuis, J. W.; ten Kate, R. W.; Soetekouw, R.; Kroon, F. P.; Arend, S. M.; de Boer, M. G. J.; van den Broek, P. J.; van Dissel, J. T.; Jolink, H.; van Nieuwkoop, C.; den Hollander, J. G.; Pogany, K.; Bronsveld, W.; Kortmann, W.; van Twillert, G.; Vriesendorp, R.; Leyten, E. M. S.; van Houte, D.; Polee, M. B.; van Vonderen, M. G. A.; ten Napel, C. H. H.; Kootstra, G. J.; Brinkman, K.; van den Berk, G. E. L.; Blok, W. L.; Frissen, P. H. J.; Schouten, W. E. M.; van Eeden, A.; Verhagen, D. W. M.; Mulder, J. W.; van Gorp, E. C. M.; Smit, P. M.; Weijer, S.; Juttmann, J. R.; Brouwer, A. E.; van Kasteren, M. E. E.; Veenstra, J.; Lettinga, K. D.; Koopmans, P. P.; Brouwer, A. M.; Dofferhoff, A. S. M.; van der Flier, M.; de Groot, R.; ter Hofstede, H. J. M.; Keuter, M.; van der Ven, A. J. A. M.; Sprenger, H. G.; van Assen, S.; Doedens, R.; Scholvinck, E. H.; Stek, C. J.; Hoepelman, A. I. M.; Arends, J. E.; Ellerbroek, P. M.; van der Hilst, J. C. H.; Jaspers, C. A. J. J.; Maarschalk-Ellerbroek, L. J.; Oosterheert, J. J.; Peters, E. J. G.; Mudrikova, T.; Schneider, M. M. E.; Wassenberg, M. W. M.; Geelen, S. P. M.; Wolfs, T. F. W.; Danner, S. A.; van Agtmael, M. A.; Bierman, W. F. W.; Claessen, F. A. P.; de Jong, E. V.; Perenboom, R. M.; bij de Vaate, E. A.; Richter, C.; van der Berg, J.; Gisolf, E. H.; van den Berge, M.; Stegeman, A.; Duits, A. J.; Winkel, K.; Abgrall, S.; Barin, F.; Bentata, M.; Billaud, E.; Boue, F.; Burty, C.; Cabie, A.; Costagliola, D.; Cotte, L.; de Truchis, P.; Duval, X.; Duvivier, C.; Enel, P.; Fredouille-Heripret, L.; Gasnault, J.; Gaud, C.; Gilquin, J.; Grabar, S.; Katlama, C.; Khuong, M. A.; Lang, J. M.; Lascaux, A. S.; Launay, O.; Mahamat, A.; Mary-Krause, M.; Matheron, S.; Meynard, J. L.; Pavie, J.; Pialoux, G.; Pilorge, F.; Poizot-Martin, I.; Pradier, C.; Reynes, J.; Rouveix, E.; Simon, A.; Tattevin, P.; Tissot-Dupont, H.; Viard, J. P.; Viget, N.; Salomon, V.; Jacquemet, N.; Guiguet, M.; Lanoy, E.; Lievre, L.; Selinger-Leneman, H.; Lacombe, J. M.; Potard, V.; Bricaire, F.; Herson, S.; Desplanque, N.; Girard, P. M.; Meyohas, M. C.; Picard, O.; Cadranel, J.; Mayaud, C.; Clauvel, J. P.; Decazes, J. M.; Gerard, L.; Molina, J. M.; Diemer, M.; Sellier, P.; Honore, P.; Jeantils, V.; Tassi, S.; Mechali, D.; Taverne, B.; Bouvet, E.; Crickx, B.; Ecobichon, J. L.; Picard-Dahan, C.; Yeni, P.; Berthe, H.; Dupont, C.; Chandemerle, C.; Mortier, E.; Tisne-Dessus, D.; Weiss, L.; Salmon, D.; Auperin, I.; Roudiere, L.; Fior, R.; Delfraissy, J. F.; Goujard, C.; Jung, C.; Lesprit, P.; Vittecoq, D.; Fraisse, P.; Rey, D.; Beck-Wirth, G.; Stahl, J. P.; Lecercq, P.; Gourdon, F.; Laurichesse, H.; Fresard, A.; Lucht, F.; Bazin, C.; Verdon, R.; Chavanet, P.; Arvieux, C.; Michelet, C.; Choutet, P.; Goudeau, A.; Maiotre, M. F.; Hoen, B.; Eglinger, P.; Faller, J. P.; Borsa-Lebas, F.; Caron, F.; Daures, J. P.; May, T.; Rabaud, C.; Berger, J. L.; Remy, G.; Arlet-Suau, E.; Cuzin, L.; Massip, P.; Thiercelin Legrand, M. F.; Pontonnier, G.; Yasdanpanah, Y.; Dellamonica, P.; Pugliese, P.; Aleksandrowicz, K.; Quinsat, D.; Ravaux, I.; Delmont, J. P.; Moreau, J.; Gastaut, J. A.; Retornaz, F.; Soubeyrand, J.; Galinier, A.; Ruiz, J. M.; Allegre, T.; Blanc, P. A.; Bonnet-Montchardon, D.; Lepeu, G.; Granet-Brunello, P.; Esterni, J. P.; Pelissier, L.; Cohen-Valensi, R.; Nezri, M.; Chadapaud, S.; Laffeuillade, A.; Raffi, F.; Boibieux, A.; Peyramond, D.; Livrozet, J. M.; Touraine, J. L.; Trepo, C.; Strobel, M.; Bissuel, F.; Pradinaud, R.; Sobesky, M.; Contant, M.; Aebi, C.; Battegay, M.; Bernasconi, E.; Boni, J.; Brazzola, P.; Bucher, H. C.; Burgisser, P.; Calmy, A.; Cattacin, S.; Cavassini, M.; Cheseaux, J. J.; Drack, G.; Dubs, R.; Egger, M.; Elzi, L.; Fischer, M.; Flepp, M.; Fontana, A.; Francioli, P.; Furrer, H. J.; Fux, C.; Gayet-Ageron, A.; Gerber, S.; Gorgievski, M.; Gunthard, H.; Gyr, T.; Hirsch, H.; Hirschel, B.; Hosli, I.; Husler, M.; Kaiser, L.; Kahlert, C.; Karrer, U.; Kind, C.; Klimkait, T.; Ledergerber, B.; Martinetti, G.; Martinez, B.; Muller, N.; Nadal, D.; Paccaud, F.; Pantaleo, G.; Raio, L.; Rauch, A.; Regenass, S.; Rickenbach, M.; Rudin, C.; Schmid, P.; Schultze, D.; Schupbach, J.; Speck, R.; Taffe, P.; Telenti, A.; Trkola, A.; Vernazza, P.; Weber, R.; Wyler, C. A.; Yerly, S.; Casabona, J.; Miro, J. M.; Alquezar, A.; Isern, V.; Esteve, A.; Podzamczer, D.; Murillas, J.; Gatell, J. M.; Aguero, F.; Tural, C.; Clotet, B.; Ferrer, E.; Riera, M.; Segura, F.; Navarro, G.; Force, L.; Vilaro, J.; Masabeu, A.; Garcia, I.; Guadarrama, M.; Romero, A.; Agusti, C.; Montoliu, A.; Ortega, N.; Lazzari, E.; Puchol, E.; Sanchez, M.; Blanco, J. L.; Garcia-Alcaide, F.; Martinez, E.; Mallolas, J.; Lopez-Dieguez, M.; Garcia-Goez, J. F.; Sirera, G.; Romeu, J.; Jou, A.; Negredo, E.; Miranda, C.; Capitan, M. C.; Olmo, M.; Barragan, P.; Saumoy, M.; Bolao, F.; Cabellos, C.; Pena, C.; Sala, M.; Cervantes, M.; Jose Amengual, M.; Navarro, M.; Penelo, E.; Barrufet, P.; Berenguer, J.; del Amo, J.; Garcia, F.; Gutierrez, F.; Labarga, P.; Moreno, S.; Munoz, M. A.; Caro-Murillo, A. M.; Sobrino, P.; Jarrin, I.; Gomez Sirvent, J. L.; Rodriguez, P.; Aleman, M. R.; Alonso, M. M.; Lopez, A. M.; Hernandez, M. I.; Soriano, V.; Barreiro, P.; Medrano, J.; Rivas, P.; Herrero, D.; Blanco, F.; Vispo, M. E.; Martin, L.; Ramirez, G.; de Diego, M.; Rubio, R.; Pulido, F.; Moreno, V.; Cepeda, C.; Hervas, R. L.; Iribarren, J. A.; Arrizabalaga, J.; Aramburu, M. J.; Camino, X.; Rodriguez-Arrondo, F.; von Wichmann, M. A.; Pascual, L.; Goenaga, M. A.; Masia, M.; Ramos, J. M.; Padilla, S.; Sanchez-Hellin, V.; Bernal, E.; Escolano, C.; Montolio, F.; Peral, Y.; Lopez, J. C.; Miralles, P.; Cosin, J.; Gutierrez, I.; Ramirez, M.; Padilla, B.; Vidal, F.; Sanjuan, M.; Peraire, J.; Veloso, S.; Vilades, C.; Lopez-Dupla, M.; Olona, M.; Vargas, M.; Aldeguer, J. L.; Blanes, M.; Lacruz, J.; Salavert, M.; Montero, M.; Cuellar, S.; de los Santos, I.; Sanz, J.; Oteo, J. A.; Blanco, J. R.; Ibarra, V.; Metola, L.; Sanz, M.; Perez-Martinez, L.; Sola, J.; Uriz, J.; Castiello, J.; Reparaz, J.; Arriaza, M. J.; Irigoyen, C.; Antela, A.; Casado, J. L.; Dronda, F.; Moreno, A.; Perez, M. J.; Lopez, D.; Gutierrez, C.; Hernandez, B.; Pumares, M.; Marti, P.; Garcia, L.; Page, C.; Hernandez, J.; Pena, A.; Munoz, L.; Parra, J.; Viciana, P.; Leal, M.; Lopez-Cortes, L. F.; Trastoy, M.; Mata, R.; Justice, A. C.; Fiellin, D. A.; Mattocks, K.; Braithwaite, S.; Brandt, C.; Bryant, K.; Cook, R.; Conigliaro, J.; Crothers, K.; Chang, J.; Crystal, S.; Day, N.; Erdos, J.; Freiberg, M.; Kozal, M.; Gandhi, N.; Gaziano, M.; Gerschenson, M.; Good, B.; Gordon, A.; Goulet, J. L.; Hernan, M. A.; Kraemer, K.; Lim, J.; Maisto, S.; Miller, P.; Mole, L.; O'Connor, P.; Papas, R.; Robins, J. M.; Rinaldo, C.; Roberts, M.; Samet, J.; Tierney, B.; Whittle, J.; Rimland, D.; Jones-Taylor, C.; Oursler, K. A.; Titanji, R.; Brown, S.; Garrison, S.; Rodriguez-Barradas, M.; Masozera, N.; Goetz, M.; Leaf, D.; Simberkoff, M.; Blumenthal, D.; Leung, J.; Butt, A.; Hoffman, E.; Gibert, C.; Peck, R.; Brettle, R.; Darbyshire, J.; Fidler, S.; Goldberg, D.; Hawkins, D.; Jaffe, H.; Johnson, A.; McLean, K.; Cursley, A.; Ewings, F.; Fairbrother, K.; Gnatiuc, L.; Lodi, S.; Murphy, B.; Smit, E.; Ward, F.; Douglas, G.; Kennedy, N.; Pritchard, J.; Andrady, U.; Rajda, N.; Maw, R.; McKernan, S.; Drake, S.; Gilleran, G.; White, D.; Ross, J.; Toomer, S.; Hewart, R.; Wilding, H.; Woodward, R.; Dean, G.; Heald, L.; Horner, P.; Glover, S.; Bansaal, D.; Eduards, S.; Carne, C.; Browing, M.; Das, R.; Stanley, B.; Estreich, S.; Magdy, A.; O'Mahony, C.; Fraser, P.; Hayman, B.; Jebakumar, S. P. R.; Joshi, U.; Ralph, S.; Wade, A.; Mette, R.; Lalik, J.; Summerfield, H.; El-Dalil, A.; France, A. J.; White, C.; Robertson, R.; Gordon, S.; McMillan, S.; Morris, S.; Lean, C.; Vithayathil, K.; McLean, L.; Winter, A.; Gale, D.; Jacobs, S.; Goorney, B.; Howard, L.; Tayal, S.; Short, L.; Green, S.; Williams, G.; Sivakumar, K.; Bhattacharyya, D. N.; Monteiro, E.; Minton, J.; Dhar, J.; Nye, F.; DeSouza, C. B.; Isaksen, A.; McDonald, L.; Franca, A.; William, L.; Jendrulek, I.; Peters, B.; Shaunak, S.; El-Gadi, S.; Easterbrook, P. J.; Mazhude, C.; Johnstone, R.; Fakoya, A.; Mchale, J.; Waters, A.; Kegg, S.; Mitchell, S.; Byrne, P.; Rice, P.; Mullaney, S. A.; McCormack, S.; David, D.; Melville, R.; Phillip, K.; Balachandran, T.; Mabey, S.; Sukthankar, A.; Murphy, C.; Wilkins, E.; Ahmad, S.; Haynes, J.; Evans, E.; Ong, E.; Grey, R.; Meaden, J.; Bignell, C.; Loay, D.; Peacock, K.; Girgis, M. R.; Morgan, B.; Palfreeman, A.; Wilcox, J.; Tobin, J.; Tucker, L.; Saeed, A. M.; Chen, F.; Deheragada, A.; Williams, O.; Lacey, H.; Herman, S.; Kinghorn, D.; Devendra, S. V.; Wither, J.; Dawson, S.; Rowen, D.; Harvey, J.; Bridgwood, A.; Singh, G.; Chauhan, M.; Kellock, D.; Young, S.; Dannino, S.; Kathir, Y.; Rooney, G.; Currie, J.; Fitzgerald, M.; Devendra, S.; Keane, F.; Booth, G.; Green, T.; Arumainayyagam, J.; Chandramani, S.; Rajamanoharan, S.; Robinson, T.; Curless, E.; Gokhale, R.; Tariq, A.; Luzzi, G.; Fairley, I.; Wallis, F.; Loze, B.; Sereni, D.; Lascoux, C.; Prevoteau, F.; Morel, P.; Timsit, J.; Oksenhendeler, E.; Morlat, P.; Bonarek, M.; Bonnet, F.; Nouts, C.; Louis, I.; Reliquet, V.; Sauser, F.; Biron, C.; Mounoury, O.; Hue, H.; Brosseau, D.; Ghosn, J.; Rannou, M. T.; Bergmann, J. F.; Badsi, E.; Rami, A.; Parrinello, M.; Samanon-Bollens, D.; Campa, P.; Tourneur, M.; Desplanques, N.; Cabane, J.; Tredup, J.; Herriot, E.; Jeanblanc, F.; Chiarello, P.; Makhloufi, D.; Blanc, A. P.; Baillat, V.; Lemoing, V.; Merle de Boever, C.; Tramoni, C.; Sobesky, G.; Abel, S.; Beaujolais, V.; Slama, L.; Chakvetadze, C.; Berrebi, V.; Fournier, I.; Gerbe, J.; Leport, C.; Jadand, C.; Jestin, C.; Longuet, P.; Boucherit, S.; Koffi, K.; Augustin-Normand, C.; Miailhes, P.; Thoirain, V.; Brochier, C.; Souala, F.; Ratajczak, M.; Montpied, G.; Beytoux, J.; Jacomet, C.; Pare, A.; Morelon, S.; Olivier, C.; Lortholary, O.; Dupont, B.; Maignan, A.; Ragnaud, J. M.; Raymond, I.; Mondor, H.; Sobel, A.; Levy, Y.; Lelievre, J. D.; Dominguez, S.; Dumont, C.; Aumaitre, H.; Delmas, B.; Saada, M.; Medus, M.; Guillevin, L.; Tahi, T.; Yazdanpanah, Y.; Pavel, S.; Marien, M. C.; Muller, E.; Drenou, B.; Beck, C.; Benomar, M.; Tubiana, R.; Ait Mohand, H.; Chermak, A.; Ben Abdallah, S.; Amirat, N.; Brancion, C.; Touam, F.; Drobacheff, C.; Folzer, A.; Obadia, M.; Prudhomme, L.; Bonnet, E.; Balzarin, F.; Pichard, E.; Chennebault, J. M.; Fialaire, P.; Loison, J.; Galanaud, P.; Bornarel, D.; Six, M.; Ferret, P.; Batisse, D.; Gonzales-Canali, G.; Devidas, A.; Chevojon, P.; Turpault, I.; Lafeuillade, A.; Cheret, A.; Philip, G.; Stein, A.; Ravault, I.; Chavanet, C.; Buisson, M.; Treuvetot, S.; Nau, P.; Bastides, F.; Boyer, L.; Wassoumbou, S.; Bernard, L.; Domart, Y.; Merrien, D.; Mignot, A.; Greder Belan, A.; Gayraud, M.; Bodard, L.; Meudec, A.; Beuscart, C.; Daniel, C.; Pape, E.; Mourier, L.; Vinceneux, P.; Simonpoli, A. M.; Zeng, A.; Jacquet, M.; Fournier, L.; Fuzibet, J. G.; Sohn, C.; Rosenthal, E.; Quaranta, M.; Chaillou, S.; Sabah, M.; Pasteur, L.; Audhuy, B.; Schieber, A.; Moreau, P.; Niault, M.; Vaillant, O.; Huchon, G.; Compagnucci, A.; de Lacroix Szmania, I.; Richier, L.; Lamaury, I.; Saint-Dizier, F.; Garipuy, D.; Drogoul, M. P.; Poizot Martin, I.; Fabre, G.; Lambert de Cursay, G.; Abraham, B.; Perino, C.; Lagarde, P.; David, F.; Veil, S.; Roche-Sicot, J.; Saraux, J. L.; Lepretre, A.; Fampin, B.; Uludag, A.; Morin, A. S.; Bletry, O.; Zucman, D.; Regnier, A.; Girard, J. J.; Quinsat, D. T.; Heripret, L.; Grihon, F.; Houlbert, D.; Ruel, M.; Chemlal, K.; Nicolle, C.; Debab, Y.; Tremollieres, F.; Perronne, V.; Duffaut, H.; Slama, B.; Perre, P.; Miodovski, C.; Guermonprez, G.; Dulioust, A.; Ballanger, R.; Boudon, P.; Malbec, D.; Patey, O.; Semaille, C.; Deville, J.; Beguinot, I.; Chambrin, V.; Pignon, C.; Estocq, G. A.; Levy, A.; Duracinsky, M.; Le Bras, P.; Ngussan, M. S.; Peretti, D.; Medintzeff, N.; Lambert, T.; Segeral, O.; Lezeau, P.; Laurian, Y.; Piketty, C.; Karmochkine, M.; Eliaszewitch, M.; Jayle, D.; Kazatchkine, M.; Colasante, U.; Nouaouia, W.; Vilde, J. L.; Bollens, D.; Binet, D.; Diallo, B.; Fonquernie, L.; Lagneau, J. L.; Pietrie, M. P.; Sicard, D.; Stieltjes, N.; Michot, J.; Bourdillon, F.; Obenga, G.; Escaut, L.; Bolliot, C.; Schneider, L.; Iguertsira, M.; Tomei, C.

    2011-01-01

    Most clinical guidelines recommend that AIDS-free, HIV-infected persons with CD4 cell counts below 0.350 × 10(9) cells/L initiate combined antiretroviral therapy (cART), but the optimal CD4 cell count at which cART should be initiated remains a matter of debate. To identify the optimal CD4 cell

  5. Rescue Therapy for Helicobacter pylori Infection 2012

    Directory of Open Access Journals (Sweden)

    Javier P. Gisbert

    2012-01-01

    Full Text Available Helicobacter pylori infection is the main cause of gastritis, gastroduodenal ulcer disease, and gastric cancer. After 30 years of experience in H. pylori treatment, however, the ideal regimen to treat this infection has still to be found. Nowadays, apart from having to know well first-line eradication regimens, we must also be prepared to face treatment failures. In designing a treatment strategy, we should not only focus on the results of primary therapy alone but also on the final—overall—eradication rate. The choice of a “rescue” treatment depends on which treatment is used initially. If a first-line clarithromycin-based regimen was used, a second-line metronidazole-based treatment (quadruple therapy may be used afterwards, and then a levofloxacin-based combination would be a third-line “rescue” option. Alternatively, it has recently been suggested that levofloxacin-based “rescue” therapy constitutes an encouraging 2nd-line strategy, representing an alternative to quadruple therapy in patients with previous PPI-clarithromycin-amoxicillin failure, with the advantage of efficacy, simplicity and safety. In this case, quadruple regimen may be reserved as a 3rd-line “rescue” option. Even after two consecutive failures, several studies have demonstrated that H. pylori eradication can finally be achieved in almost all patients if several “rescue” therapies are consecutively given.

  6. Vacuum-assisted closure therapy for infected perineal wounds after abdominoperineal resection. A retrospective cohort study.

    Science.gov (United States)

    Walma, M S; Burbach, J P M; Verheijen, P M; Pronk, A; van Grevenstein, W M U

    2016-02-01

    Perineal wound complications are a main problem after abdominoperineal resection (APR). There is little evidence concerning perineal wound management. This study describes and evaluates the role of vacuum-assisted closure (VAC) therapy in wound management strategies of perineal wound infections after APR. Patients undergoing APR for malignant disease between January 2007 and January 2013 were identified retrospectively. Data regarding occurrence and management of perineal wound complications were collected. Perineal wound infections were classified into minor or major complications and time to wound healing was measured. Time to wound healing was compared between patients receiving routine care or with additional VAC therapy. Of 171 included patients, 76 (44.4%) had minor and 36 (21.1%) major perineal wound infections. Management of major infected perineal wounds consisted of drainage (n = 16), debridement (n = 4), drainage combined with debridement (n = 4), VAC therapy alone (n = 5), or VAC therapy combined with other treatments (n = 7). Median duration of perineal wound healing in major infected wounds was 141 days (range 17-739). Median time to wound healing was not different in patients treated with (172 days, range 23-368) or without VAC therapy (131 days, range 17-739). In this study, VAC therapy did not shorten time to wound healing. However, prospective studies are required to investigate the role of VAC therapy in management of infected perineal wounds after APR. Up to then, wound management will remain to be based on clinical perception and 'gut-feeling'. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

  7. Dose De-escalation of Intrapleural Tissue Plasminogen Activator Therapy for Pleural Infection. The Alteplase Dose Assessment for Pleural Infection Therapy Project.

    Science.gov (United States)

    Popowicz, Natalia; Bintcliffe, Oliver; De Fonseka, Duneesha; Blyth, Kevin G; Smith, Nicola A; Piccolo, Francesco; Martin, Geoffrey; Wong, Donny; Edey, Anthony; Maskell, Nick; Lee, Y C Gary

    2017-06-01

    Intrapleural therapy with a combination of tissue plasminogen activator (tPA) 10 mg and DNase 5 mg administered twice daily has been shown in randomized and open-label studies to successfully manage over 90% of patients with pleural infection without surgery. Potential bleeding risks associated with intrapleural tPA and its costs remain important concerns. The aim of the ongoing Alteplase Dose Assessment for Pleural infection Therapy (ADAPT) project is to investigate the efficacy and safety of dose de-escalation for intrapleural tPA. The first of several planned studies is presented here. To evaluate the efficacy and safety of a reduced starting dose regimen of 5 mg of tPA with 5 mg of DNase administered intrapleurally for pleural infection. Consecutive patients with pleural infection at four participating centers in Australia, the United Kingdom, and New Zealand were included in this observational, open-label study. Treatment was initiated with tPA 5 mg and DNase 5 mg twice daily. Subsequent dose escalation was permitted at the discretion of the attending physician. Data relating to treatment success, radiological and systemic inflammatory changes (blood C-reactive protein), volume of fluid drained, length of hospital stay, and treatment complications were extracted retrospectively from the medical records. We evaluated 61 patients (41 males; age, 57 ± 16 yr). Most patients (n = 58 [93.4%]) were successfully treated without requiring surgery for pleural infection. Treatment success was corroborated by clearance of pleural opacities visualized by chest radiography (from 42% [interquartile range, 22-58] to 16% [8-31] of hemithorax; P < 0.001), increase in pleural fluid drainage (from 175 ml in the 24 h preceding treatment to 2,025 ml [interquartile range, 1,247-2,984] over 72 h of therapy; P <  0.05) and a reduction in blood C-reactive protein (P < 0.05). Seven patients (11.5%) had dose escalation of tPA to 10 mg. Three patients underwent

  8. PUVA combination therapy.

    Science.gov (United States)

    Morison, W L

    1985-08-01

    Various adjunctive treatments are now frequently used in combination with PUVA therapy with the aims of limiting adverse effects, improving efficacy and decreasing the cost of treatment. In the management of psoriasis, PUVA plus retinoids, PUVA plus methotrexate and PUVA plus UVB phototherapy are the most frequently used combinations. PUVA plus topical corticosteroids and PUVA plus anthralin are also efficacious but adverse effects and poor acceptance by patients are limiting factors. Combinations of PUVA plus nitrogen mustard and ionizing radiation are used in mycosis fungoides to treat tumors and residual disease in secluded sites. In the management of photodermatoses with PUVA therapy, prednisone is often required to prevent exacerbation of disease. A combination of prednisone and PUVA therapy can also be useful in lichen planus and atopic eczema. The selection of a suitable combination treatment, will depend upon the preferences of the clinician, the disease being treated, and the characteristics of the patient.

  9. Antitussive pharmaceutical drugs administration in complex therapy of acute respiratory infections in children

    OpenAIRE

    Lokshina, E.; Zajtseva, O.

    2009-01-01

    There is considered the problem of treatment of cough in children with acute respiratory infections in article. In particular, the data on an effective administration of the domestic combined medication framed on basis of medicinal grasses with codeine in complex therapy of acute respiratory infections is presented.

  10. Curcumin-arteether combination therapy of Plasmodium berghei-infected mice prevents recrudescence through immunomodulation.

    Directory of Open Access Journals (Sweden)

    Palakkod G Vathsala

    Full Text Available Earlier studies in this laboratory have shown the potential of artemisinin-curcumin combination therapy in experimental malaria. In a parasite recrudescence model in mice infected with Plasmodium berghei (ANKA, a single dose of alpha,beta-arteether (ART with three oral doses of curcumin prevented recrudescence, providing almost 95% protection. The parasites were completely cleared in blood with ART-alone (AE or ART+curcumin (AC treatments in the short-term, although the clearance was faster in the latter case involving increased ROS generation. But, parasites in liver and spleen were not cleared in AE or AC treatments, perhaps, serving as a reservoir for recrudescence. Parasitemia in blood reached up to 60% in AE-treated mice during the recrudescence phase, leading to death of animals. A transient increase of up to 2-3% parasitemia was observed in AC-treatment, leading to protection and reversal of splenomegaly. A striking increase in spleen mRNA levels for TLR2, IL-10 and IgG-subclass antibodies but a decrease in those for INFγ and IL-12 was observed in AC-treatment. There was a striking increase in IL-10 and IgG subclass antibody levels but a decrease in INFγ levels in sera leading to protection against recrudescence. AC-treatment failed to protect against recrudescence in TLR2(-/- and IL-10(-/- animals. IL-10 injection to AE-treated wild type mice and AC-treated TLR2(-/- mice was able to prolong survival. Blood from the recrudescence phase in AE-treatment, but not from AC-treatment, was able to reinfect and kill naïve animals. Sera from the recrudescence phase of AC-treated animals reacted with several parasite proteins compared to that from AE-treated animals. It is proposed that activation of TLR2-mediated innate immune response leading to enhanced IL-10 production and generation of anti-parasite antibodies contribute to protective immunity in AC-treated mice. These results indicate a potential for curcumin-based combination therapy to

  11. Antiviral therapy and prophylaxis of acute respiratory infections

    Directory of Open Access Journals (Sweden)

    L. V. Osidak

    2012-01-01

    Full Text Available Thearticle presents the results of years of studies (including biochemical and immunological of the effectiveness of application and prophylaxis (in relation to nosocomial infections and the safety of antiviral chemical preparation Arbidol in 694 children with influenza and influenza-like illness, including the coronavirus infection (43 children and combined lesions of respiratory tract (150, indicating the possible inclusion of the drug in the complex therapy for children with the listed diseases, regardless of the severity and nature of their course. The studies were conducted according to the regulated standard of test conditions and randomized clinical trials.

  12. Artemether-Lumefantrine Combination Therapy for Treatment of Uncomplicated Malaria: The Potential for Complex Interactions with Antiretroviral Drugs in HIV-Infected Individuals

    Directory of Open Access Journals (Sweden)

    Pauline Byakika-Kibwika

    2011-01-01

    Full Text Available Treatment of malaria in HIV-infected individuals receiving antiretroviral therapy (ART poses significant challenges. Artemether-lumefantrine (AL is one of the artemisisnin-based combination therapies recommended for treatment of malaria. The drug combination is highly efficacious against sensitive and multidrug resistant falciparum malaria. Both artemether and lumefantrine are metabolized by hepatic cytochrome P450 (CYP450 enzymes which metabolize the protease inhibitors (PIs and nonnucleoside reverse transcriptase inhibitors (NNRTIs used for HIV treatment. Coadministration of NNRTIs and PIs with AL could potentially cause complex pharmacokinetic drug interactions. NNRTI by inducing CYP450 3A4 enzyme and PIs by inhibiting CYP450 3A4 enzymes could influence both artemether and lumefantrine concentrations and their active metabolites dihydroartemisinin and desbutyl-lumefantrine, predisposing patients to poor treatment response, toxicity, and risk for development of resistance. There are scanty data on these interactions and their consequences. Pharmacokinetic studies to evaluate these interactions in the target populations are urgently needed.

  13. MODERN APPROACHES TO THE THERAPY OF VIRAL PAPILLOMA SKIN INFECTION IN INFANCY

    Directory of Open Access Journals (Sweden)

    L.K. Aslamazian

    2006-01-01

    Full Text Available To improve the methods of prevention and treatment of viral papilloma infection, the researchers examined 80 children, suffering from skin forms of a disease. They examined peculiarities of a disease and interferon status of all the children. The data of clinic and laboratory research allowed them to assume that viral papilloma infection grows along with the reduction of immune mechanisms and it grows among the children, suffering from the genetic burden to viral diseases. All the patients, suffering from the disorder of interferon status, have undergone the complex therapy, which included medications of recombinant interferon (Viferon in suppositories and extrinsic. For the first time, the researchers removed the skin papillomas by a combination method: cryofreezing and photovaporization. The analysis of treatment and observation within a year and a half showed that in a group of children, who received a combination treatment, including Viferon therapy and removal of verrucas by 2 surgical methods. No backset of a disease detected. In general, the findings of the research pointed out the high efficiency of topical and systemic Viferon medications, as well as combination method of verruca removal in complex treatment of viral papilloma skin infection among the children.Key words: interferon status of children, interferon al'fa 2b, verrucas, viral papilloma infection.

  14. Synergistic Interaction Between Phage Therapy and Antibiotics Clears Pseudomonas Aeruginosa Infection in Endocarditis and Reduces Virulence.

    Science.gov (United States)

    Oechslin, Frank; Piccardi, Philippe; Mancini, Stefano; Gabard, Jérôme; Moreillon, Philippe; Entenza, José M; Resch, Gregory; Que, Yok-Ai

    2017-03-01

    Increasing antibiotic resistance warrants therapeutic alternatives. Here we investigated the efficacy of bacteriophage-therapy (phage) alone or combined with antibiotics against experimental endocarditis (EE) due to Pseudomonas aeruginosa, an archetype of difficult-to-treat infection. In vitro fibrin clots and rats with aortic EE were treated with an antipseudomonas phage cocktail alone or combined with ciprofloxacin. Phage pharmacology, therapeutic efficacy, and resistance were determined. In vitro, single-dose phage therapy killed 7 log colony-forming units (CFUs)/g of fibrin clots in 6 hours. Phage-resistant mutants regrew after 24 hours but were prevented by combination with ciprofloxacin (2.5 × minimum inhibitory concentration). In vivo, single-dose phage therapy killed 2.5 log CFUs/g of vegetations in 6 hours (P 6 log CFUs/g of vegetations in 6 hours and successfully treating 64% (n = 7/11) of rats. Phage-resistant mutants emerged in vitro but not in vivo, most likely because resistant mutations affected bacterial surface determinants important for infectivity (eg, the pilT and galU genes involved in pilus motility and LPS formation). Single-dose phage therapy was active against P. aeruginosa EE and highly synergistic with ciprofloxacin. Phage-resistant mutants had impaired infectivity. Phage-therapy alone or combined with antibiotics merits further clinical consideration. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

  15. Effects of treatment with suppressive combination antiretroviral drug therapy and the histone deacetylase inhibitor suberoylanilide hydroxamic acid; (SAHA on SIV-infected Chinese rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Binhua Ling

    Full Text Available Viral reservoirs-persistent residual virus despite combination antiretroviral therapy (cART-remain an obstacle to cure of HIV-1 infection. Difficulty studying reservoirs in patients underscores the need for animal models that mimics HIV infected humans on cART. We studied SIV-infected Chinese-origin rhesus macaques (Ch-RM treated with intensive combination antiretroviral therapy (cART and 3 weeks of treatment with the histone deacetyalse inhibitor, suberoylanilide hydroxamic acid (SAHA.SIVmac251 infected Ch-RM received reverse transcriptase inhibitors PMPA and FTC and integrase inhibitor L-870812 beginning 7 weeks post infection. Integrase inhibitor L-900564 and boosted protease inhibitor treatment with Darunavir and Ritonavir were added later. cART was continued for 45 weeks, with daily SAHA administered for the last 3 weeks, followed by euthanasia/necropsy. Plasma viral RNA and cell/tissue-associated SIV gag RNA and DNA were quantified by qRT-PCR/qPCR, with flow cytometry monitoring changes in immune cell populations.Upon cART initiation, plasma viremia declined, remaining <30 SIV RNA copy Eq/ml during cART, with occasional blips. Decreased viral replication was associated with decreased immune activation and partial restoration of intestinal CD4+ T cells. SAHA was well tolerated but did not result in demonstrable treatment-associated changes in plasma or cell associated viral parameters.The ability to achieve and sustain virological suppression makes cART-suppressed, SIV-infected Ch-RM a potentially useful model to evaluate interventions targeting residual virus. However, despite intensive cART over one year, persistent viral DNA and RNA remained in tissues of all three animals. While well tolerated, three weeks of SAHA treatment did not demonstrably impact viral RNA levels in plasma or tissues; perhaps reflecting dosing, sampling and assay limitations.

  16. Beta-lactam combination therapy for the treatment of Staphylococcus aureus and Enterococcus species bacteremia: A summary and appraisal of the evidence

    Directory of Open Access Journals (Sweden)

    Rachel Bartash

    2017-10-01

    Full Text Available Staphylococcal bacteremia and enterococcal bacteremia are prevalent in hospitalized or recently instrumented patients, and are associated with significant morbidity and mortality. They are often difficult to treat due to the pathogenicity of the organisms, poor response to antibiotics, and increasing development of multidrug resistance. Therefore, there has been increasing interest in combination therapy for the treatment of these infections. The aim of this review was to summarize and assess the evidence supporting combination beta-lactam therapy for both Staphylococcus aureus and Enterococcus species blood stream infections. Currently, there is promising in vitro data but little clinical evidence supporting combination beta-lactam therapy for this indication. Further clinical investigations are needed to elucidate the potential benefits of beta-lactam combination therapy over monotherapy for Gram-positive bacteremia, although combination therapy may be useful in refractory cases of bacteremia that do not respond to standard antibiotic therapy.

  17. Increasing use of artemisinin-based combination therapy for treatment of malaria infection in Nigerian hospitals

    Directory of Open Access Journals (Sweden)

    Igboeli NU

    2010-12-01

    Full Text Available Objectives: This study aimed at describing the pattern of outpatient antimalarial drug prescribing in a secondary and a tertiary hospital, and to assess adherence to the National Antimalarial Treatment Guideline (ATG. Methods: An audit of antimalarial prescription files from the two health facilities for a period of six months in 2008 was conducted. Semi structured questionnaires were used to collect information from the doctors and pharmacists on their awareness and knowledge of the National Antimalarial Treatment Guideline. Results: Artemisinin-based combination therapies (ACTs were the most prescribed antimalarials. Overall, 81.4% of the total prescriptions contained ACTs, out of which 56.8% were artemether-lumefantrine. However, adherence to the drugs indicated by national guideline within the DU90% was 38.5% for the tertiary and 66.7 % for the secondary hospital. The standard practice of prescribing with generic name was still not adhered to as evidenced in the understudied hospitals. The percentage of health care providers that were aware of the ATG was 88.2% for doctors and 85.1% for pharmacists. However, 13.3% and 52.2% of doctors and pharmacists respectively could not properly list the drugs specified in the guideline. Amodiaquine was the most commonly preferred option for managing children aged 0 – 3 months with malaria infection against the indicated oral quinine.Conclusion: This study showed an increased use of artemisinin-based combination therapy for the treatment of uncomplicated malaria compared previous reports in Nigeria. This study also highlights the need for periodic in-service quality assurance among health professionals with monitoring of adherence to and assessment of knowledge of clinical guidelines to ensure the practice of evidence based medicine.

  18. Combination antiretroviral therapy improves cognitive performance and functional connectivity in treatment-naïve HIV-infected individuals.

    Science.gov (United States)

    Zhuang, Yuchuan; Qiu, Xing; Wang, Lu; Ma, Qing; Mapstone, Mark; Luque, Amneris; Weber, Miriam; Tivarus, Madalina; Miller, Eric; Arduino, Roberto C; Zhong, Jianhui; Schifitto, Giovanni

    2017-10-01

    Our study aimed to investigate the short-term effect of combination antiretroviral therapy (cART) on cognitive performance and functional and structural connectivity and their relationship to plasma levels of antiretroviral (ARV) drugs. Seventeen ARV treatment-naïve HIV-infected individuals (baseline mean CD4 cell count, 479 ± 48 cells/mm 3 ) were age matched with 17 HIV-uninfected individuals. All subjects underwent a detailed neurocognitive and functional assessment and magnetic resonance imaging. HIV-infected subjects were scanned before starting cART and 12 weeks after initiation of treatment. Uninfected subjects were assessed once at baseline. Functional connectivity (FC) was assessed within the default mode network while structural connectivity was assessed by voxel-wise analysis using tract-based spatial statistics (TBSS) and probabilistic tractography within the DMN. Tenofovir and emtricitabine blood concentration were measured at week 12 of cART. Prior to cART, HIV-infected individuals had significantly lower cognitive performance than control subjects as measured by the total Z-score from the neuropsychological tests assessing six cognitive domains (p = 0.020). After 12 weeks of cART treatment, there remained only a weak cognitive difference between HIV-infected and HIV-uninfected subjects (p = 0.057). Mean FC was lower in HIV-infected individuals compared with those uninfected (p = 0.008), but FC differences became non-significant after treatment (p = 0.197). There were no differences in DTI metrics between HIV-infected and HIV-uninfected individuals using the TBSS approach and limited evidence of decreased structural connectivity within the DMN in HIV-infected individuals. Tenofovir and emtricitabine plasma concentrations did not correlate with either cognitive performance or imaging metrics. Twelve weeks of cART improves cognitive performance and functional connectivity in ARV treatment-naïve HIV-infected individuals with relatively

  19. Polyclonal Antibody Therapies for Clostridium difficile Infection

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    Michael R. Simon

    2014-10-01

    Full Text Available Clostridium difficile infection has emerged as a growing worldwide health problem. The colitis of Clostridium difficile infection results from the synergistic action of C. difficile secreted toxins A and B upon the colon mucosa. A human monoclonal IgG anti-toxin has demonstrated the ability in combination therapy to reduce mortality in C. difficile challenged hamsters. This antibody is currently in a clinical trial for the treatment of human Clostridium difficile infection. More than one group of investigators has considered using polyclonal bovine colostral antibodies to toxins A and B as an oral passive immunization. A significant proportion of the healthy human population possesses polyclonal antibodies to the Clostridium difficile toxins. We have demonstrated that polyclonal IgA derived from the pooled plasma of healthy donors possesses specificity to toxins A and B and can neutralize these toxins in a cell-based assay. This suggests that secretory IgA prepared from such pooled plasma IgA may be able to be used as an oral treatment for Clostridium difficile infection.

  20. Herpes simplex virus type 2 (HSV-2) genital shedding in HSV-2-/HIV-1-co-infected women receiving effective combination antiretroviral therapy.

    Science.gov (United States)

    Péré, Héléne; Rascanu, Aida; LeGoff, Jérome; Matta, Mathieu; Bois, Frédéric; Lortholary, Olivier; Leroy, Valériane; Launay, Odile; Bélec, Laurent

    2016-03-01

    The dynamics of genital shedding of HSV-2 DNA was assessed in HIV-1-infected women taking combination antiretroviral therapy (cART). HIV-1 RNA, HIV-1 DNA and HSV DNA loads were measured during 12-18 months using frozen plasma, PBMC and cervicovaginal lavage samples from 22 HIV-1-infected women, including 17 women naive for antiretroviral therapy initiating cART and 5 women with virological failure switching to a new regimen. Nineteen (86%) women were HSV-2-seropositive. Among HSV-2-/HIV-1-co-infected women, HIV-1 RNA loads showed a rapid fall from baseline after one month of cART, in parallel in paired plasma and cervicovaginal secretions. In contrast, HIV-1 DNA loads did not show significant variations from baseline up to 18 months of treatment in both systemic and genital compartments. HSV DNA was detected at least once in 12 (63%) of 19 women during follow up: HSV-2 shedding in the genital compartment was observed in 11% of cervicovaginal samples at baseline and in 16% after initiating or switching cART. Cervicovaginal HIV-1 RNA loads were strongly associated with plasma HIV-1 RNA loads over time, but not with cervicovaginal HSV DNA loads. Reactivation of genital HSV-2 replication frequently occurred despite effective cART in HSV-2-/HIV-1-co-infected women. Genital HSV-2 replication under cART does not influence cervicovaginal HIV-1 RNA or DNA shedding. © The Author(s) 2015.

  1. Study of the effect of antiviral therapy on homocysteinemia in hepatitis C virus- infected patients

    Directory of Open Access Journals (Sweden)

    Mustafa Mubin

    2012-08-01

    Full Text Available Abstract Background Hepatitis C virus (HCV infection is one of the leading causes of chronic liver disease (CLD. About 80% of those exposed to the virus develop a chronic infection. Hyperhomocysteinemia, which is an independent risk factor for atherosclerotic vascular disease and thromboembolism, may develop in HCV-infected patients although altered alanine amino transferase (ALT enzyme levels are generally associated with damage to liver cells. The gold standard therapy for chronic hepatitis C patients is pegylated interferon combined with an anti-viral drug (ribavirin. The current study aimed to investigate the effect of antiviral therapy on plasma homocysteine (Hcy levels in HCV patients in addition to other parameters. Methods 532 HCV-infected patients and 70 healthy controls were recruited for the study. All patients were subjected to laboratory investigations including HCV-RNA levels, complete blood cell counts, serum levels of homocysteine, ALT, alkaline phosphatase (ALP, lipid profile and liver ultrasonographic examination. The outcome of treatment with pegylated interferon α plus ribavirin treatment and sustained virologic response (SVR was determined 6–9 months post-therapy. Results Hyperhomocysteinemia was found in 91.35% of HCV-infected patients. The difference in plasma Hcy concentrations reached statistical significance between the patient and control groups. ALT, cholesterol and triglycerides (TGs levels were found higher than normal in the patients group. After receiving a combined therapy for 24 weeks, 43.66% patients showed an SVR (responders; 30.98% patients were non-responders while 25.35% patients initially responded to therapy but again retrieved positive status of HCV infection six months post-therapy (relapse-cirrhotic patients. The mean levels of plasma Hcy, ALT and ALP were significantly reduced in responders within 10 weeks of therapy when compared with non-responders and relapse-cirrhotic patients. Conclusion

  2. Incidence and timing of cancer in HIV-infected individuals following initiation of combination antiretroviral therapy.

    Science.gov (United States)

    Yanik, Elizabeth L; Napravnik, Sonia; Cole, Stephen R; Achenbach, Chad J; Gopal, Satish; Olshan, Andrew; Dittmer, Dirk P; Kitahata, Mari M; Mugavero, Michael J; Saag, Michael; Moore, Richard D; Mayer, Kenneth; Mathews, W Christopher; Hunt, Peter W; Rodriguez, Benigno; Eron, Joseph J

    2013-09-01

    Cancer is an important cause of morbidity and mortality in individuals infected with human immunodeficiency virus (HIV), but patterns of cancer incidence after combination antiretroviral therapy (ART) initiation remain poorly characterized. We evaluated the incidence and timing of cancer diagnoses among patients initiating ART between 1996 and 2011 in a collaboration of 8 US clinical HIV cohorts. Poisson regression was used to estimate incidence rates. Cox regression was used to identify demographic and clinical characteristics associated with cancer incidence after ART initiation. At initiation of first combination ART among 11 485 patients, median year was 2004 (interquartile range [IQR], 2000-2007) and median CD4 count was 202 cells/mm(3) (IQR, 61-338). Incidence rates for Kaposi sarcoma (KS) and lymphomas were highest in the first 6 months after ART initiation (P cancers combined increased from 416 to 615 cases per 100 000 person-years from 1 to 10 years after ART initiation (average 7% increase per year; 95% confidence interval, 2%-13%). Lower CD4 count at ART initiation was associated with greater risk of KS, lymphoma, and human papillomavirus-related cancer. Calendar year of ART initiation was not associated with cancer incidence. KS and lymphoma rates were highest immediately following ART initiation, particularly among patients with low CD4 cell counts, whereas other cancers increased with time on ART, likely reflecting increased cancer risk with aging. Our results underscore recommendations for earlier HIV diagnosis followed by prompt ART initiation along with ongoing aggressive cancer screening and prevention efforts throughout the course of HIV care.

  3. Combination of anti-retroviral drugs and radioimmunotherapy specifically kills infected cells from HIV infected individuals

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    Dina Tsukrov

    2016-09-01

    Full Text Available Eliminating virally infected cells is an essential component of any HIV eradication strategy. Radioimmunotherapy (RIT, a clinically established method for killing cells using radiolabeled antibodies, was recently applied to target HIV-1 gp41 antigen expressed on the surface of infect-ed cells. Since gp41 expression by infected cells is likely down-regulated in patients on an-tiretroviral therapy (ART, we evaluated the ability of RIT to kill ART-treated infected cells us-ing both in vitro models and lymphocytes isolated from HIV-infected subjects. Human peripheral blood mononuclear cells (PBMCs were infected with HIV and cultured in the presence of two clinically relevant ART combinations. Scatchard analysis of the 2556 human monoclonal anti-body to HIV gp41 binding to the infected and ART-treated cells demonstrated sufficient residual expression of gp41 on the cell surface to warrant subsequent RIT. This is the first time the quantification of gp41 post-ART is being reported. Cells were then treated with Bismuth-213-labeled 2556 antibody. conjugated to the human monoclonal antibody 2556, which binds to HIV gp41. Cell survival was quantified by Trypan blue and residual viremia by p24 ELISA. Cell surface gp41 expression was assessed by Scatchard analysis. The experiments were repeated using PBMCs isolated from blood specimens obtained from 15 HIV-infected individuals: ten on ART and five ART-naive. We found that 213Bi-2556 killed ART-treated infected PBMCs and reduced viral production to undetectable levels. ART and RIT co-treatment was more effective at reducing viral load in vitro than either therapy alone, indicating that gp41 expression under ART was sufficient to allow 213Bi-2556 to deliver cytocidal doses of radiation to infected cells. This study provides proof of concept that 213Bi-2556 may represent an innovative and effective targeting method for killing HIV-infected cells treated with ART, and supports continued development of 213Bi

  4. Kaposi Sarcoma Risk in HIV-Infected Children and Adolescents on Combination Antiretroviral Therapy From Sub-Saharan Africa, Europe, and Asia

    DEFF Research Database (Denmark)

    Rohner, Eliane; Schmidlin, Kurt; Zwahlen, Marcel

    2016-01-01

    . RESULTS:  We included 24 991 children from eastern Africa, southern Africa, Europe and Asia; 26 developed KS after starting cART. Incidence rates per 100 000 person-years (PYs) were 86 in eastern Africa (95% confidence interval [CI], 55-133), 11 in southern Africa (95% CI, 4-35), and 81 (95% CI, 26......HR, 3.4; 95% CI, 1.2-10.1) and advanced HIV/AIDS stage (CDC stage C vs A/B; aHR, 2.4; 95% CI, .8-7.3) at cART initiation. CONCLUSIONS:  HIV-infected children from SSA but not those from other regions, have a high risk of developing KS after cART initiation. Early cART initiation in these children might......BACKGROUND:  The burden of Kaposi sarcoma (KS) in human immunodeficiency virus (HIV)-infected children and adolescents on combination antiretroviral therapy (cART) has not been compared globally. METHODS:  We analyzed cohort data from the International Epidemiologic Databases to Evaluate AIDS...

  5. Efficacy and Safety of Metronidazole Monotherapy versus Vancomycin Monotherapy or Combination Therapy in Patients with Clostridium difficile Infection: A Systematic Review and Meta-Analysis.

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    Rui Li

    Full Text Available Clostridium difficile infection (CDI has become a global epidemiological problem for both hospitalized patients and outpatients. The most commonly used drugs to treat CDI are metronidazole and vancomycin. The aim of this study was to compare the efficacy and safety of metronidazole monotherapy with vancomycin monotherapy and combination therapy in CDI patients.A comprehensive search without publication status or other restrictions was conducted. Studies comparing metronidazole monotherapy with vancomycin monotherapy or combination therapy in patients with CDI were considered eligible. Meta-analysis was performed using the Mantel-Haenszel fixed-effects model, and odds ratios (ORs with 95% confidence intervals (95% CIs were calculated and reported.Of the 1910 records identified, seventeen studies from thirteen articles (n = 2501 patients were included. No statistically significant difference in the rate of clinical cure was found between metronidazole and vancomycin for mild CDI (OR = 0.67, 95% CI (0.45, 1.00, p = 0.05 or between either monotherapy and combination therapy for CDI (OR = 1.07, 95% CI (0.58, 1.96, p = 0.83; however, the rate of clinical cure was lower for metronidazole than for vancomycin for severe CDI (OR = 0.46, 95% CI (0.26, 0.80, p = 0.006. No statistically significant difference in the rate of CDI recurrence was found between metronidazole and vancomycin for mild CDI (OR = 0.99, 95% CI (0.40, 2.45, p = 0.98 or severe CDI (OR = 0.98, 95% CI (0.63, 1.53, p = 0.94 or between either monotherapy and combination therapy for CDI (OR = 0.91, 95% CI (0.66, 1.26, p = 0.56. In addition, there was no significant difference in the rate of adverse events (AEs between metronidazole and vancomycin (OR = 1.18, 95% CI (0.80, 1.74, p = 0.41. In contrast, the rate of AEs was significantly lower for either monotherapy than for combination therapy (OR = 0.30, 95% CI (0.17, 0.51, p < 0.0001.Metronidazole and vancomycin are equally effective for the

  6. Artemisinin versus nonartemisinin combination therapy for uncomplicated malaria: randomized clinical trials from four sites in Uganda.

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    Adoke Yeka

    2005-07-01

    Full Text Available BACKGROUND: Drug resistance in Plasmodium falciparum poses a major threat to malaria control. Combination antimalarial therapy including artemisinins has been advocated recently to improve efficacy and limit the spread of resistance, but artemisinins are expensive and relatively untested in highly endemic areas. We compared artemisinin-based and other combination therapies in four districts in Uganda with varying transmission intensity. METHODS AND FINDINGS: We enrolled 2,160 patients aged 6 mo or greater with uncomplicated falciparum malaria. Patients were randomized to receive chloroquine (CQ + sulfadoxine-pyrimethamine (SP; amodiaquine (AQ + SP; or AQ + artesunate (AS. Primary endpoints were the 28-d risks of parasitological failure either unadjusted or adjusted by genotyping to distinguish recrudescence from new infections. A total of 2,081 patients completed follow-up, of which 1,749 (84% were under the age of 5 y. The risk of recrudescence after treatment with CQ + SP was high, ranging from 22% to 46% at the four sites. This risk was significantly lower (p < 0.01 after AQ + SP or AQ + AS (7%-18% and 4%-12%, respectively. Compared to AQ + SP, AQ + AS was associated with a lower risk of recrudescence but a higher risk of new infection. The overall risk of repeat therapy due to any recurrent infection (recrudescence or new infection was similar at two sites and significantly higher for AQ + AS at the two highest transmission sites (risk differences = 15% and 16%, p < 0.003. CONCLUSION: AQ + AS was the most efficacious regimen for preventing recrudescence, but this benefit was outweighed by an increased risk of new infection. Considering all recurrent infections, the efficacy of AQ + SP was at least as efficacious at all sites and superior to AQ + AS at the highest transmission sites. The high endemicity of malaria in Africa may impact on the efficacy of artemisinin-based combination therapy. The registration number for this trial is ISRCTN

  7. Artemisinin versus Nonartemisinin Combination Therapy for Uncomplicated Malaria: Randomized Clinical Trials from Four Sites in Uganda

    Science.gov (United States)

    Yeka, Adoke; Banek, Kristin; Bakyaita, Nathan; Staedke, Sarah G; Kamya, Moses R; Talisuna, Ambrose; Kironde, Fred; Nsobya, Samuel L; Kilian, Albert; Slater, Madeline; Reingold, Arthur; Rosenthal, Philip J; Wabwire-Mangen, Fred; Dorsey, Grant

    2005-01-01

    Background Drug resistance in Plasmodium falciparum poses a major threat to malaria control. Combination antimalarial therapy including artemisinins has been advocated recently to improve efficacy and limit the spread of resistance, but artemisinins are expensive and relatively untested in highly endemic areas. We compared artemisinin-based and other combination therapies in four districts in Uganda with varying transmission intensity. Methods and Findings We enrolled 2,160 patients aged 6 mo or greater with uncomplicated falciparum malaria. Patients were randomized to receive chloroquine (CQ) + sulfadoxine-pyrimethamine (SP); amodiaquine (AQ) + SP; or AQ + artesunate (AS). Primary endpoints were the 28-d risks of parasitological failure either unadjusted or adjusted by genotyping to distinguish recrudescence from new infections. A total of 2,081 patients completed follow-up, of which 1,749 (84%) were under the age of 5 y. The risk of recrudescence after treatment with CQ + SP was high, ranging from 22% to 46% at the four sites. This risk was significantly lower (p AQ + SP or AQ + AS (7%–18% and 4%–12%, respectively). Compared to AQ + SP, AQ + AS was associated with a lower risk of recrudescence but a higher risk of new infection. The overall risk of repeat therapy due to any recurrent infection (recrudescence or new infection) was similar at two sites and significantly higher for AQ + AS at the two highest transmission sites (risk differences = 15% and 16%, pAQ + AS was the most efficacious regimen for preventing recrudescence, but this benefit was outweighed by an increased risk of new infection. Considering all recurrent infections, the efficacy of AQ + SP was at least as efficacious at all sites and superior to AQ + AS at the highest transmission sites. The high endemicity of malaria in Africa may impact on the efficacy of artemisinin-based combination therapy. The registration number for this trial is ISRCTN67520427 (http

  8. Maggot therapy in treatment of a complex hand injury complicated by mycotic infection.

    Science.gov (United States)

    Bohac, M; Cambal, M; Zamborsky, R; Takac, P; Fedeles, J

    2015-01-01

    Complex injuries of the hand remain a therapeutic challenge for surgeons. We present the case of a male who suffered a devastating injury of the hand caused by a conveyor belt. The patient developed a progressive Absidia corymbifera infection of the affected soft tissues. Initial treatments with serial surgical debridement and topical and intravenous itraconazole were unsuccessful in eliminating the infection. We decided to use maggot debridement therapy in a new special design to debride all necrotic, devitalized tissue and preserve only healthy tissue and functioning structures. This maneuverer followed by negative pressure therapy allowed progressive healing. In such complex hand injuries, maggot debridement combined with negative pressure therapy could be considered to achieve effective and considerable results, although future functional morbidity may occur (Fig. 4, Ref. 18).

  9. Phase II study of bevacizumab and temsirolimus combination therapy for recurrent glioblastoma multiforme

    DEFF Research Database (Denmark)

    Lassen, Ulrik; Sorensen, Morten; Gaziel, Tine Bernhardtsen

    2013-01-01

    standard temozolomide chemoradiotherapy and bevacizumab-containing second-line therapy, received temsirolimus (25 mg i.v.) on days 1 and 8 and bevacizumab (10 mg/kg) on day 8, every two weeks. Assessments were performed every eight weeks. Blood samples for biomarkers were collected weekly for the first...... eight weeks and at progression. The primary end-point was median progression-free survival (PFS) and secondary end-points were radiographic response, overall survival (OS), and safety of the bevacizumab-temsirolimus combination. RESULTS: Thirteen patients were included, whereof three went off....../10), infection (1/10), hypertension (1/10), and hyperglycemia (1/10). CONCLUSION: Temsirolimus can be safely administered in combination with bevacizumab. This study failed to detect activity of such a combination in patients with progressive GBM beyond bevacizumab therapy....

  10. Fatal infections in older patients with inflammatory bowel disease on anti-tumor necrosis factor therapy

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    Way-Seah Lee

    2017-10-01

    Full Text Available Anti-tumor necrosis factor (anti-TNF is highly effective in inflammatory bowel disease (IBD; however, it is associated with an increased risk of infections, particularly in older adults. We reviewed 349 patients with IBD, who were observed over a 12-month period, 74 of whom had received anti-TNF therapy (71 patients were aged <60 years and 3 were aged ≥60 years. All the 3 older patients developed serious infectious complications after receiving anti-TNFs, although all of them were also on concomitant immunosuppressive therapy. One patient developed disseminated tuberculosis, another patient developed cholera diarrhea followed by nosocomial pneumonia, while the third patient developed multiple opportunistic infections (Pneumocystis pneumonia, cryptococcal septicemia and meningitis, Klebsiella septicemia. All 3 patients died within 1 year from the onset of the infection(s. We recommend that anti-TNF, especially when combined with other immunosuppressive therapy, should be used with extreme caution in older adult patients with IBD.

  11. Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Carbapenem-Resistant Organisms

    Science.gov (United States)

    Temkin, Elizabeth; Torre-Cisneros, Julian; Beovic, Bojana; Benito, Natividad; Giannella, Maddalena; Gilarranz, Raúl; Jeremiah, Cameron; Loeches, Belén; Machuca, Isabel; Jiménez-Martín, María José; Martínez, José Antonio; Mora-Rillo, Marta; Navas, Enrique; Osthoff, Michael; Pozo, Juan Carlos; Ramos Ramos, Juan Carlos; Rodriguez, Marina; Sánchez-García, Miguel; Viale, Pierluigi; Wolff, Michel

    2016-01-01

    ABSTRACT Ceftazidime-avibactam (CAZ-AVI) is a recently approved β-lactam–β-lactamase inhibitor combination with the potential to treat serious infections caused by carbapenem-resistant organisms. Few patients with such infections were included in the CAZ-AVI clinical trials, and clinical experience is lacking. We present a case series of patients with infections caused by carbapenem-resistant Enterobacteriaceae (CRE) or Pseudomonas aeruginosa (CRPa) who were treated with CAZ-AVI salvage therapy on a compassionate-use basis. Physicians who had prescribed CAZ-AVI completed a case report form. We used descriptive statistics to summarize patient characteristics and treatment outcomes. We used the Wilcoxon rank sum test and Fisher's exact test to compare patients by treatment outcome. The sample included 36 patients infected with CRE and two with CRPa. The most common infections were intra-abdominal. Physicians categorized 60.5% of patients as having life-threatening infections. All but two patients received other antibiotics before CAZ-AVI, for a median of 13 days. The median duration of CAZ-AVI treatment was 16 days. Twenty-five patients (65.8%) concurrently received other antibiotics to which their pathogen was nonresistant in vitro. Twenty-eight patients (73.7%, 95% confidence interval [CI], 56.9 to 86.6%) experienced clinical and/or microbiological cure. Five patients (20.8%) with documented microbiological cure died, whereas 10 patients (71.4%) with no documented microbiological cure died (P = 0.01). In three-quarters of cases, CAZ-AVI (alone or combined with other antibiotics) cured infections caused by carbapenem-resistant organisms, 95% of which had failed previous therapy. Microbiological cure was associated with improved survival. CAZ-AVI shows promising clinical results for infections for which treatment options are limited. PMID:27895014

  12. Strongyloides Hyperinfection Syndrome Combined with Cytomegalovirus Infection

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    Fatehi Elnour Elzein

    2016-01-01

    Full Text Available The mortality in Strongyloides hyperinfection syndrome (SHS is alarmingly high. This is particularly common in bone marrow, renal, and other solid organ transplant (SOT patients, where figures may reach up to 50–85%. Immunosuppressives, principally corticosteroids, are the primary triggering factor. In general, the clinical features of Strongyloides stercoralis hyperinfection are nonspecific; therefore, a high index of suspicion is required for early diagnosis and starting appropriate therapy. Although recurrent Gram-negative sepsis and meningitis have been previously reported, the combination of both cytomegalovirus (CMV and strongyloidiasis had rarely been associated. We here describe a patient who survived SHS with recurrent Escherichia coli (E. coli urosepsis and CMV infection.

  13. Living situation affects adherence to combination antiretroviral therapy in HIV-infected adolescents in Rwanda: a qualitative study.

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    Philippe R Mutwa

    Full Text Available INTRODUCTION: Adherence to combination antiretroviral therapy (cART is vital for HIV-infected adolescents for survival and quality of life. However, this age group faces many challenges to remain adherent. We used multiple data sources (role-play, focus group discussions (FGD, and in-depth interviews (IDI to better understand adherence barriers for Rwandan adolescents. Forty-two HIV positive adolescents (ages 12-21 and a selection of their primary caregivers were interviewed. All were perinatally-infected and received (cART for ≥ 12 months. Topics discussed during FGDs and IDIs included learning HIV status, disclosure and stigma, care and treatment issues, cART adherence barriers. RESULTS: Median age was 17 years, 45% female, 45% orphaned, and 48% in boarding schools. We identified three overarching but inter-related themes that appeared to influence adherence. Stigma, perceived and experienced, and inadvertent disclosure of HIV status hampered adolescents from obtaining and taking their drugs, attending clinic visits, carrying their cARTs with them in public. The second major theme was the need for better support, in particular for adolescents with different living situations, (orphanages, foster-care, and boarding schools. Lack of privacy to keep and take medication came out as major barrier for adolescents living in congested households, as well the institutionalization of boarding schools where privacy is almost non-existent. The third important theme was the desire to be 'normal' and not be recognized as an HIV-infected individual, and to have a normal life not perturbed by taking a regimen of medications or being forced to disclose where others would treat them differently. CONCLUSIONS: We propose better management of HIV-infected adolescents integrated into boarding school, orphanages, and foster care; training of school-faculty on how to support students and allow them privacy for taking their medications. To provide better care and

  14. Immunosuppressive therapy in non-infections uveitis and retinovasculitis

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    E. A. Drozdova

    2014-07-01

    Full Text Available Purpose: to evaluate the efficacy and safety of the immunosuppressive therapy for severe forms of non-infections uveitis and retinovasculitis.Methods: 107 patients (62 males and 45 females aged 9 to 54 years who received low dose methotrexate — 7.5-20 mg once a week (n=79 cyclosporine A 3.5-5.0 mg/kg/d (n=21 with prednisone or other antimetabolites and local corticosteroid therapy for severe forms of inflammatory eye diseases.Results: the efficacy of methotrexate as monotherapy was 51.8% of patients with chronic uveitis. Control of acute inflammation was achived in 71.1% patients, who received methotrexate in combination with prednisolone. Cyclosporine A was more effective in controlling inflammatory of the eye: remission of uveitis was achived in 85.7% in combination with glucocorticoids. No significant side effects have been noted.Conclusion: Methotrexate and cyclosporine A with low dose of prednisolone are well tolerated immunosuppressive agents andrather effective in the treatment of non-infectious uveitis and retinovasculitis that fails to respond to conventional steroid treatment.

  15. Immunosuppressive therapy in non-infections uveitis and retinovasculitis

    Directory of Open Access Journals (Sweden)

    E. A. Drozdova

    2012-01-01

    Full Text Available Purpose: to evaluate the efficacy and safety of the immunosuppressive therapy for severe forms of non-infections uveitis and retinovasculitis.Methods: 107 patients (62 males and 45 females aged 9 to 54 years who received low dose methotrexate — 7.5-20 mg once a week (n=79 cyclosporine A 3.5-5.0 mg/kg/d (n=21 with prednisone or other antimetabolites and local corticosteroid therapy for severe forms of inflammatory eye diseases.Results: the efficacy of methotrexate as monotherapy was 51.8% of patients with chronic uveitis. Control of acute inflammation was achived in 71.1% patients, who received methotrexate in combination with prednisolone. Cyclosporine A was more effective in controlling inflammatory of the eye: remission of uveitis was achived in 85.7% in combination with glucocorticoids. No significant side effects have been noted.Conclusion: Methotrexate and cyclosporine A with low dose of prednisolone are well tolerated immunosuppressive agents andrather effective in the treatment of non-infectious uveitis and retinovasculitis that fails to respond to conventional steroid treatment.

  16. Chemotherapy and molecular target therapy combined with radiation therapy

    International Nuclear Information System (INIS)

    Akimoto, Tetsuo

    2012-01-01

    Combined chemotherapy and radiation therapy has been established as standard treatment approach for locally advanced head and neck cancer, esophageal cancer and so on through randomized clinical trials. However, radiation-related morbidity such as acute toxicity also increased as treatment intensity has increased. In underlining mechanism for enhancement of normal tissue reaction in chemo-radiation therapy, chemotherapy enhanced radiosensitivity of normal tissues in addition to cancer cells. Molecular target-based drugs combined with radiation therapy have been expected as promising approach that makes it possible to achieve cancer-specific enhancement of radiosensitivity, and clinical trials using combined modalities have been performed to evaluate the feasibility and efficacy of this approach. In order to obtain maximum radiotherapeutic gain, a detailed understanding of the mechanism underlying the interaction between radiation and Molecular target-based drugs is indispensable. Among molecular target-based drugs, inhibitors targeting epidermal growth factor receptor (EGFR) and its signal transduction pathways have been vigorously investigated, and mechanisms regarding the radiosensitizing effect have been getting clear. In addition, the results of randomized clinical trials demonstrated that radiation therapy combined with cetuximab resulted in improvement of overall and disease-specific survival rate compared with radiation therapy in locally advanced head and neck cancer. In this review, clinical usefulness of chemo-radiation therapy and potential molecular targets for potentiation of radiation-induced cell killing are summarized. (author)

  17. Modeling antibiotic treatment in hospitals: A systematic approach shows benefits of combination therapy over cycling, mixing, and mono-drug therapies.

    Science.gov (United States)

    Tepekule, Burcu; Uecker, Hildegard; Derungs, Isabel; Frenoy, Antoine; Bonhoeffer, Sebastian

    2017-09-01

    Multiple treatment strategies are available for empiric antibiotic therapy in hospitals, but neither clinical studies nor theoretical investigations have yielded a clear picture when which strategy is optimal and why. Extending earlier work of others and us, we present a mathematical model capturing treatment strategies using two drugs, i.e the multi-drug therapies referred to as cycling, mixing, and combination therapy, as well as monotherapy with either drug. We randomly sample a large parameter space to determine the conditions determining success or failure of these strategies. We find that combination therapy tends to outperform the other treatment strategies. By using linear discriminant analysis and particle swarm optimization, we find that the most important parameters determining success or failure of combination therapy relative to the other treatment strategies are the de novo rate of emergence of double resistance in patients infected with sensitive bacteria and the fitness costs associated with double resistance. The rate at which double resistance is imported into the hospital via patients admitted from the outside community has little influence, as all treatment strategies are affected equally. The parameter sets for which combination therapy fails tend to fall into areas with low biological plausibility as they are characterised by very high rates of de novo emergence of resistance to both drugs compared to a single drug, and the cost of double resistance is considerably smaller than the sum of the costs of single resistance.

  18. Ribavirin-induced anemia in hepatitis C virus patients undergoing combination therapy.

    Directory of Open Access Journals (Sweden)

    Sheeja M Krishnan

    2011-02-01

    Full Text Available The current standard of care for hepatitis C virus (HCV infection - combination therapy with pegylated interferon and ribavirin - elicits sustained responses in only ∼50% of the patients treated. No alternatives exist for patients who do not respond to combination therapy. Addition of ribavirin substantially improves response rates to interferon and lowers relapse rates following the cessation of therapy, suggesting that increasing ribavirin exposure may further improve treatment response. A key limitation, however, is the toxic side-effect of ribavirin, hemolytic anemia, which often necessitates a reduction of ribavirin dosage and compromises treatment response. Maximizing treatment response thus requires striking a balance between the antiviral and hemolytic activities of ribavirin. Current models of viral kinetics describe the enhancement of treatment response due to ribavirin. Ribavirin-induced anemia, however, remains poorly understood and precludes rational optimization of combination therapy. Here, we develop a new mathematical model of the population dynamics of erythrocytes that quantitatively describes ribavirin-induced anemia in HCV patients. Based on the assumption that ribavirin accumulation decreases erythrocyte lifespan in a dose-dependent manner, model predictions capture several independent experimental observations of the accumulation of ribavirin in erythrocytes and the resulting decline of hemoglobin in HCV patients undergoing combination therapy, estimate the reduced erythrocyte lifespan during therapy, and describe inter-patient variations in the severity of ribavirin-induced anemia. Further, model predictions estimate the threshold ribavirin exposure beyond which anemia becomes intolerable and suggest guidelines for the usage of growth hormones, such as erythropoietin, that stimulate erythrocyte production and avert the reduction of ribavirin dosage, thereby improving treatment response. Our model thus facilitates, in

  19. Effects of antiretroviral therapy on immunity in patients infected with HIV.

    Science.gov (United States)

    Feola, D J; Thornton, A C; Garvy, B A

    2006-01-01

    Drug therapy for human immunodeficiency virus (HIV) is highly effective in suppressing viral replication and restoring immune function in patients with HIV. However, this same treatment can also be associated with immunotoxicity. For example, zidovudine and various other antiretroviral agents are capable of causing bone marrow suppression. Agents used to treat opportunistic infections in these individuals, including ganciclovir, foscarnet, and sulfamethoxazole-trimethoprim, can cause additional hematotoxicity. Drug-drug interactions must also be considered and managed in order to control iatrogenic causes of immunotoxicity. In this review, we examine the normal immune response to HIV, and the benefits of antiretroviral therapy in prolonging immune function. We then discuss immune-related adverse effects of drugs used to treat HIV and the opportunistic infections that are common among these patients. Finally, we address in vitro, animal, and clinical evidence of toxicity associated with various combination use of these agents.

  20. [Therapeutic effects of a combination treatment with flomoxef and tobramycin against infections complicated with hematological disorders].

    Science.gov (United States)

    Yamane, T; Tanaka, K; Hasuike, T; Hirai, M; Misu, K; Ota, K; Ohira, H; Nakao, Y; Yasui, Y; Inoue, T

    1992-08-01

    The efficacy and safety of a combination regimen using flomoxef (FMOX) and tobramycin (TOB) were evaluated in the treatment of infections complicated with hematological disorders. The primary diseases in 40 patients included acute leukemia, malignant lymphoma and others. Complicated infections included 35 cases with suspected septicemia, 4 cases with septicemia and 1 case with pleuritis. Clinical responses were excellent in 10 (25.0%), good in 14 (35.0%), fair in 2 (5.0%) and poor in 14 (35.0%). The efficacy rate was 73.1% in patients with neutrophil counts higher than 501/microliters after administration, but it was 35.7% in patients with counts less than 501/microliters; the difference was statistically significant. No side effects were observed in any of the 40 patients. Abnormal laboratory data in liver functions were identified in 1 patient (2.5%). Degree of this abnormality was very slight, and the continuation of treatment was not disturbed. In conclusion, this combination therapy of FMOX and TOB thus appears to be useful and safe in therapies for infections complicated with hematological disorders.

  1. BIOCHEMICAL SUBSTANTIATION OF COMBINED THERAPY APPLICATION IN THE ACUTE PHASE OF EXPERIMENTAL HELMINTHIASIS OF ANIMALS

    Directory of Open Access Journals (Sweden)

    E. A. Grishina

    2017-01-01

    Full Text Available The purpose of this study was to investigate the influence of the invasion process and different strategies of treatment on some biochemical blood indices of mice infested with Syphacia obvelata and Trichocephalus muris of gastrointestinal tract, in order to optimize etiotropic therapy and improve its efficiency. Materials and methods. In the experiment were used albino mice, divided into the following groups: intact animals (control group; animals infected with Syphacia obvelata; animals infected with Trichocephalus muris; infected animals, who received a single dose of albendazole (7 mg/kg; infected animals, who received a single dose of albendazole (7 mg/kg and gamavit dose intramuscularly (0.3 cm3/kg simultaneously. Blood for the studies was taken from the animals at 1, 3, 7, 10, 14, 17, 21 days after the infection and after drug administration. From biochemical parameters were determined activities of next enzymes: alanine aminotransferase (ALT, aspartate aminotransferase (AST, gamma-glutamyl transferase (γ-GTP and alkaline phosphatase (AP – with kinetic method IFCC. Results. Infecting animals with helminthes caused a noticeable increase in AP and gamma-GTP levels and cytolytic activity of enzymes: ALT and AST compared with intact group. The above-mentioned complex of metabolic changes clearly reveals a disturbance in hepatocyte metabolism that leads to the decrease in detoxifying function of the liver. This can be apparently explained with toxic effects of helminthes waste products. Albendazole mono-therapy in the therapeutic dose (7 mg/kg of mice infected with both Syphacia and Trichocephalus caused an even greater increase in ALT and AST levels and also increased serum levels of alkaline phosphatase and γ-GTP, compared with the control and infected animals, that clearly shows an additional toxic effect from the antihelmintic drug. The use of albendazole in combination with a complex antioxidant “Gamavit” in animals infected with

  2. Effect of cytomegalovirus co-infection on normalization of selected T-cell subsets in children with perinatally acquired HIV infection treated with combination antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Suad Kapetanovic

    Full Text Available We examined the effect of cytomegalovirus (CMV co-infection and viremia on reconstitution of selected CD4+ and CD8+ T-cell subsets in perinatally HIV-infected (PHIV+ children ≥ 1-year old who participated in a partially randomized, open-label, 96-week combination antiretroviral therapy (cART-algorithm study.Participants were categorized as CMV-naïve, CMV-positive (CMV+ viremic, and CMV+ aviremic, based on blood, urine, or throat culture, CMV IgG and DNA polymerase chain reaction measured at baseline. At weeks 0, 12, 20 and 40, T-cell subsets including naïve (CD62L+CD45RA+; CD95-CD28+, activated (CD38+HLA-DR+ and terminally differentiated (CD62L-CD45RA+; CD95+CD28- CD4+ and CD8+ T-cells were measured by flow cytometry.Of the 107 participants included in the analysis, 14% were CMV+ viremic; 49% CMV+ aviremic; 37% CMV-naïve. In longitudinal adjusted models, compared with CMV+ status, baseline CMV-naïve status was significantly associated with faster recovery of CD8+CD62L+CD45RA+% and CD8+CD95-CD28+% and faster decrease of CD8+CD95+CD28-%, independent of HIV VL response to treatment, cART regimen and baseline CD4%. Surprisingly, CMV status did not have a significant impact on longitudinal trends in CD8+CD38+HLA-DR+%. CMV status did not have a significant impact on any CD4+ T-cell subsets.In this cohort of PHIV+ children, the normalization of naïve and terminally differentiated CD8+ T-cell subsets in response to cART was detrimentally affected by the presence of CMV co-infection. These findings may have implications for adjunctive treatment strategies targeting CMV co-infection in PHIV+ children, especially those that are now adults or reaching young adulthood and may have accelerated immunologic aging, increased opportunistic infections and aging diseases of the immune system.

  3. Effect of cytomegalovirus co-infection on normalization of selected T-cell subsets in children with perinatally acquired HIV infection treated with combination antiretroviral therapy.

    Science.gov (United States)

    Kapetanovic, Suad; Aaron, Lisa; Montepiedra, Grace; Anthony, Patricia; Thuvamontolrat, Kasalyn; Pahwa, Savita; Burchett, Sandra; Weinberg, Adriana; Kovacs, Andrea

    2015-01-01

    We examined the effect of cytomegalovirus (CMV) co-infection and viremia on reconstitution of selected CD4+ and CD8+ T-cell subsets in perinatally HIV-infected (PHIV+) children ≥ 1-year old who participated in a partially randomized, open-label, 96-week combination antiretroviral therapy (cART)-algorithm study. Participants were categorized as CMV-naïve, CMV-positive (CMV+) viremic, and CMV+ aviremic, based on blood, urine, or throat culture, CMV IgG and DNA polymerase chain reaction measured at baseline. At weeks 0, 12, 20 and 40, T-cell subsets including naïve (CD62L+CD45RA+; CD95-CD28+), activated (CD38+HLA-DR+) and terminally differentiated (CD62L-CD45RA+; CD95+CD28-) CD4+ and CD8+ T-cells were measured by flow cytometry. Of the 107 participants included in the analysis, 14% were CMV+ viremic; 49% CMV+ aviremic; 37% CMV-naïve. In longitudinal adjusted models, compared with CMV+ status, baseline CMV-naïve status was significantly associated with faster recovery of CD8+CD62L+CD45RA+% and CD8+CD95-CD28+% and faster decrease of CD8+CD95+CD28-%, independent of HIV VL response to treatment, cART regimen and baseline CD4%. Surprisingly, CMV status did not have a significant impact on longitudinal trends in CD8+CD38+HLA-DR+%. CMV status did not have a significant impact on any CD4+ T-cell subsets. In this cohort of PHIV+ children, the normalization of naïve and terminally differentiated CD8+ T-cell subsets in response to cART was detrimentally affected by the presence of CMV co-infection. These findings may have implications for adjunctive treatment strategies targeting CMV co-infection in PHIV+ children, especially those that are now adults or reaching young adulthood and may have accelerated immunologic aging, increased opportunistic infections and aging diseases of the immune system.

  4. Enhancing virus-specific immunity in vivo by combining therapeutic vaccination and PD-L1 blockade in chronic hepadnaviral infection.

    Directory of Open Access Journals (Sweden)

    Jia Liu

    2014-01-01

    Full Text Available Hepatitis B virus (HBV persistence is facilitated by exhaustion of CD8 T cells that express the inhibitory receptor programmed cell death-1 (PD-1. Improvement of the HBV-specific T cell function has been obtained in vitro by inhibiting the PD-1/PD-ligand 1 (PD-L1 interaction. In this study, we examined whether in vivo blockade of the PD-1 pathway enhances virus-specific T cell immunity and leads to the resolution of chronic hepadnaviral infection in the woodchuck model. The woodchuck PD-1 was first cloned, characterized, and its expression patterns on T cells from woodchucks with acute or chronic woodchuck hepatitis virus (WHV infection were investigated. Woodchucks chronically infected with WHV received a combination therapy with nucleoside analogue entecavir (ETV, therapeutic DNA vaccination and woodchuck PD-L1 antibody treatment. The gain of T cell function and the suppression of WHV replication by this therapy were evaluated. We could show that PD-1 expression on CD8 T cells was correlated with WHV viral loads during WHV infection. ETV treatment significantly decreased PD-1 expression on CD8 T cells in chronic carriers. In vivo blockade of PD-1/PD-L1 pathway on CD8 T cells, in combination with ETV treatment and DNA vaccination, potently enhanced the function of virus-specific T cells. Moreover, the combination therapy potently suppressed WHV replication, leading to sustained immunological control of viral infection, anti-WHs antibody development and complete viral clearance in some woodchucks. Our results provide a new approach to improve T cell function in chronic hepatitis B infection, which may be used to design new immunotherapeutic strategies in patients.

  5. Antifibrotic Therapy in Simian Immunodeficiency Virus Infection Preserves CD4+ T-Cell Populations and Improves Immune Reconstitution With Antiretroviral Therapy

    Science.gov (United States)

    Estes, Jacob D.; Reilly, Cavan; Trubey, Charles M.; Fletcher, Courtney V.; Cory, Theodore J.; Piatak, Michael; Russ, Samuel; Anderson, Jodi; Reimann, Thomas G.; Star, Robert; Smith, Anthony; Tracy, Russell P.; Berglund, Anna; Schmidt, Thomas; Coalter, Vicky; Chertova, Elena; Smedley, Jeremy; Haase, Ashley T.; Lifson, Jeffrey D.; Schacker, Timothy W.

    2015-01-01

    Even with prolonged antiretroviral therapy (ART), many human immunodeficiency virus-infected individuals have <500 CD4+ T cells/µL, and CD4+ T cells in lymphoid tissues remain severely depleted, due in part to fibrosis of the paracortical T-cell zone (TZ) that impairs homeostatic mechanisms required for T-cell survival. We therefore used antifibrotic therapy in simian immunodeficiency virus-infected rhesus macaques to determine whether decreased TZ fibrosis would improve reconstitution of peripheral and lymphoid CD4+ T cells. Treatment with the antifibrotic drug pirfenidone preserved TZ architecture and was associated with significantly larger populations of CD4+ T cells in peripheral blood and lymphoid tissues. Combining pirfenidone with an ART regimen was associated with greater preservation of CD4+ T cells than ART alone and was also associated with higher pirfenidone concentrations. These data support a potential role for antifibrotic drug treatment as adjunctive therapy with ART to improve immune reconstitution. PMID:25246534

  6. IP-10 predicts the first phase decline of HCV RNA and overall viral response to therapy in patients co-infected with chronic hepatitis C virus infection and HIV

    DEFF Research Database (Denmark)

    Falconer, Karolin; Askarieh, Galia; Weis, Nina Margrethe

    2010-01-01

    The aim of this study was to investigate the utility of baseline plasma interferon-gamma inducible protein-10 (IP-10) levels in human immunodeficiency virus (HIV)-hepatitis C virus (HCV) co-infected patients. Baseline IP-10 was monitored during HCV combination therapy in 21 HIV-HCV co-infected...... patients (HCV genotype 1 (n = 16), 2 (n = 2), and 3 (n = 3)). Lower baseline IP-10 was significantly associated with a rapid decline in HCV RNA, in particular with the first phase reduction, and similar cut-off levels ( 600 pg/ml) as in HCV mono-infected patients apply. In conclusion, baseline IP......-10 infected patients, and may thus be useful in encouraging such difficult-to-treat patients to initiate therapy....

  7. Effects of glucocorticoid combined with antibiotics on serum infection indexes, acute phase proteins and stress hormones in patients with severe pneumonia

    Directory of Open Access Journals (Sweden)

    Yang Yu

    2017-10-01

    Full Text Available Objective: To study the effects of glucocorticoid combined with antibiotics on serum infection indexes, acute phase proteins and stress hormones in patients with severe pneumonia. Methods: a total of 80 patients with severe pneumonia who were hospitalized between August 2014 and January 2017 were retrospectively analyzed and divided into the routine treatment group (n=46 who received conventional antibiotic therapy and the combined treatment group (n=34 who received glucocorticoid combined with antibiotic therapy, and the differences in infection indexes, acute proteins and stress hormones were compared between the two groups of patients before and after treatment. Results: The differences in serum levels of infection indexes, acute phase proteins and stress hormones were not statistically significant between the two groups before treatment. After 1 week of treatment, serum infection indexes CRP and PCT levels of observation group were lower than those of control group; serum acute phase proteins α1-AT, α1-AG and CER levels were lower than those of control group; serum stress hormones Cor, AngⅠ and AngⅡ levels were lower than those of control group. Conclusion: Glucocorticoid combined with antibiotics can effectively inhibit systemic infection and stress and optimize the illness in patients with severe pneumonia.

  8. Dual beta-lactam therapy for serious Gram-negative infections: is it time to revisit?

    Science.gov (United States)

    Rahme, Christine; Butterfield, Jill M; Nicasio, Anthony M; Lodise, Thomas P

    2014-12-01

    We are rapidly approaching a crisis in antibiotic resistance, particularly among Gram-negative pathogens. This, coupled with the slow development of novel antimicrobial agents, underscores the exigency of redeploying existing antimicrobial agents in innovative ways. One therapeutic approach that was heavily studied in the 1980s but abandoned over time is dual beta-lactam therapy. This article reviews the evidence for combination beta-lactam therapy. Overall, in vitro, animal and clinical data are positive and suggest that beta-lactam combinations produce a synergistic effect against Gram-negative pathogens that rivals that of beta-lactam-aminoglycoside or beta-lactam-fluoroquinolone combination therapy. Although the precise mechanism of improved activity is not completely understood, it is likely attributable to an enhanced affinity to the diverse penicillin-binding proteins found among Gram negatives. The collective data indicate that dual beta-lactam therapy should be revisited for serious Gram-negative infections, especially in light of the near availability of potent beta-lactamase inhibitors, which neutralize the effect of problematic beta-lactamases. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Co-therapy using lytic bacteriophage and linezolid: effective treatment in eliminating methicillin resistant Staphylococcus aureus (MRSA from diabetic foot infections.

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    Sanjay Chhibber

    Full Text Available BACKGROUND: Staphylococcus aureus remains the predominant pathogen in diabetic foot infections and prevalence of methicillin resistant S.aureus (MRSA strains further complicates the situation. The incidence of MRSA in infected foot ulcers is 15-30% and there is an alarming trend for its increase in many countries. Diabetes acts as an immunosuppressive state decreasing the overall immune functioning of body and to worsen the situation, wounds inflicted with drug resistant strains represent a morbid combination in diabetic patients. Foot infections caused by MRSA are associated with an increased risk of amputations, increased hospital stay, increased expenses and higher infection-related mortality. Hence, newer, safer and effective treatment strategies are required for treating MRSA mediated diabetic foot infections. The present study focuses on the use of lytic bacteriophage in combination with linezolid as an effective treatment strategy against foot infection in diabetic population. METHODOLOGY: Acute hindpaw infection with S.aureus ATCC 43300 was established in alloxan induced diabetic BALB/c mice. Therapeutic efficacy of a well characterized broad host range lytic bacteriophage, MR-10 was evaluated alone as well as in combination with linezolid in resolving the course of hindpaw foot infection in diabetic mice. The process of wound healing was also investigated. RESULTS AND CONCLUSIONS: A single administration of phage exhibited efficacy similar to linezolid in resolving the course of hindpaw infection in diabetic animals. However, combination therapy using both the agents was much more effective in arresting the entire infection process (bacterial load, lesion score, foot myeloperoxidase activity and histopathological analysis. The entire process of tissue healing was also hastened. Use of combined agents has been known to decrease the frequency of emergence of resistant mutants, hence this approach can serve as an effective strategy in

  10. Current trends in local antibacterial therapy of periprosthetic infection and osteomyelitis

    Directory of Open Access Journals (Sweden)

    S. A. Bozhkova

    2015-01-01

    Full Text Available The rational use of antibiotics in the treatment of orthopedic infection still presents a significant problem. Local antibiotic delivery systems enable to achieve effective concentrations of drugs in the focus of bone infection without the development of toxicity. It is the important accompaniment to systemic antibiotics in the treatment of periprosthetic infection and osteomyelitis. The data collected through the PubMed and eLIBRARY databases (http://www.ncbi.nlm. nih.gov/pubmed, 1995-2015; http://elibrary.ru, 2005-2015 years present the information about bone substitutes used for local antibiotic therapy in scientific investigations and in clinical practice. The information is submitted in accordance with the groups of materials: cements based on polymethylmethacrylate, bone grafts, demineralized bone matrix, bioceramics, natural and synthetic polymers, combined antibiotic delivery systems. The majority of these materials have only been studied experimentally and only a limited range of them is registered for use in clinical practice. Informing orthopedic surgeons about current methods of local antibiotic use is the key to the development of a modern integrated approach to the therapy of infectious complications after orthopedic surgery.

  11. Impact of round-the-clock CSF Gram stain on empirical therapy for suspected central nervous system infections.

    Science.gov (United States)

    Tissot, F; Prod'hom, G; Manuel, O; Greub, G

    2015-09-01

    The impact of round-the-clock cerebrospinal fluid (CSF) Gram stain on overnight empirical therapy for suspected central nervous system (CNS) infections was investigated. All consecutive overnight CSF Gram stains between 2006 and 2011 were included. The impact of a positive or a negative test on empirical therapy was evaluated and compared to other clinical and biological indications based on institutional guidelines. Bacterial CNS infection was documented in 51/241 suspected cases. Overnight CSF Gram stain was positive in 24/51. Upon validation, there were two false-positive and one false-negative results. The sensitivity and specificity were 41 and 99 %, respectively. All patients but one had other indications for empirical therapy than Gram stain alone. Upon obtaining the Gram result, empirical therapy was modified in 7/24, including the addition of an appropriate agent (1), addition of unnecessary agents (3) and simplification of unnecessary combination therapy (3/11). Among 74 cases with a negative CSF Gram stain and without formal indication for empirical therapy, antibiotics were withheld in only 29. Round-the-clock CSF Gram stain had a low impact on overnight empirical therapy for suspected CNS infections and was associated with several misinterpretation errors. Clinicians showed little confidence in CSF direct examination for simplifying or withholding therapy before definite microbiological results.

  12. Opportunistic infections and AIDS malignancies early after initiating combination antiretroviral therapy in high-income countries

    NARCIS (Netherlands)

    Lodi, Sara; Del Amo, Julia; Moreno, Santiago; Bucher, Heiner C.; Furrer, Hansjakob; Logan, Roger; Sterne, Jonathan; Pérez-Hoyos, Santiago; Jarrín, Inma; Phillips, Andrew; Olson, Ashley; Van Sighem, Ard; Reiss, Peter; Sabin, Caroline; Jose, Sophie; Justice, Amy; Goulet, Joseph; Miró, José M.; Ferrer, Elena; Meyer, Laurence; Seng, Rémonie; Vourli, Georgia; Antoniadou, Anastasia; Dabis, Francois; Vandenhede, Mari-Anne; Costagliola, Dominique; Abgrall, Sophie; Hernán, Miguel A.; Hernan, Miguel; Bansi, L.; Hill, T.; Sabin, C.; Dunn, D.; Porter, K.; Glabay, A.; Orkin, C.; Thomas, R.; Jones, K.; Fisher, M.; Perry, N.; Pullin, A.; Churchill, D.; Gazzard, B.; Nelson, M.; Asboe, D.; Bulbeck, S.; Mandalia, S.; Clarke, J.; Delpech, V.; Anderson, J.; Munshi, S.; Post, F.; Easterbrook, P.; Khan, Y.; Patel, P.; Karim, F.; Duffell, S.; Gilson, R.; Man, S.-L.; Williams, I.; Gompels, M.; Dooley, D.; Schwenk, A.; Ainsworth, J.; Johnson, M.; Youle, M.; Lampe, F.; Smith, C.; Grabowska, H.; Chaloner, C.; Ismajani Puradiredja, D.; Bansi, L.; Hill, T.; Phillips, A.; Sabin, C.; Walsh, J.; Weber, J.; Kemble, C.; Mackie, N.; Winston, A.; Leen, C.; Wilson, A.; Bezemer, D.O.; Gras, L.A.J.; Kesselring, A.M.; Van Sighem, A.I.; Zaheri, S.; Van Twillert, G.; Kortmann, W.; Branger, J.; Prins, J.M.; Kuijpers, T.W.; Scherpbier, H.J.; Van Der Meer, J.T.M.; Wit, F.W.M.N.; Godfried, M.H.; Reiss, P.; Van Der Poll, T.; Nellen, F.J.B.; Lange, J.M.A.; Geerlings, S.E.; Van Vugt, M.; Pajkrt, D.; Bos, J.C.; van der Valk, M.; Grijsen, M.L.; Wiersinga, W.J.; Brinkman, K.; Blok, W.L.; Frissen, P.H.J.; Schouten, W.E.M.; Van Den Berk, G.E.L.; Veenstra, J.; Lettinga, K.D.; Mulder, J.W.; Vrouenraets, S.M.E.; Lauw, F.N.; Van Eeden, A.; Verhagen, D.W.M.; Van Agtmael, M.A.; Perenboom, R.M.; Claessen, F.A.P.; Bomers, M.; Peters, E.J.G.; Richter, C.; Van Der Berg, J.P.; Gisolf, E.H.; Schippers, E.F.; Van Nieuwkoop, C.; Van Elzakker, E.P.; Leyten, E.M.S.; Gelinck, L.B.S.; Pronk, M.J.H.; Bravenboer, B.; Kootstra, G.J.; Delsing, C.E.; Sprenger, H.G.; Doedens, R.; Scholvinck, E.H.; Van Assen, S.; Bierman, W.F.W.; Soetekouw, R.; Ten Kate, R.W.; Van Vonderen, M.G.A.; Van Houte, D.P.F.; Kroon, F.P.; Van Dissel, J.T.; Arend, S.M.; De Boer, M.G.J.; Jolink, H.; Ter Vollaard, H.J.M.; Bauer, M.P.; Weijer, S.; El Moussaoui, R.; Lowe, S.; Schreij, G.; Oude Lashof, A.; Posthouwer, D.; Koopmans, P.P.; Keuter, M.; Van Der Ven, A.J.A.M.; Ter Hofstede, H.J.M.; Dofferhoff, A.S.M.; Warris, A.; Van Crevel, R.; van der Ende, Marchina E.; De Vries-Sluijs, T.E.M.S.; Schurink, C.A.M.; Nouwen, J.L.; Nispen Tot Pannerden, M.H.; Verbon, A.; Rijnders, B.J.A.; Van Gorp, E.C.M.; Hassing, R.J.; Smeulders, A.W.M.; Hartwig, N.G.; Driessen, G.J.A.; Den Hollander, J.G.; Pogany, K.; Juttmann, J.R.; Van Kasteren, M.E.E.; Hoepelman, A.I.M.; Mudrikova, T.; Schneider, M.M.E.; Jaspers, C.A.J.J.; Ellerbroek, P.M.; Oosterheert, J.J.; Arends, J.E.; Wassenberg, M.W.M.; Barth, R.E.; Geelen, S.P.M.; Wolfs, T.F.W.; Bont, L.J.; Van Den Berge, M.; Stegeman, A.; Groeneveld, P.H.P.; Alleman, M.A.; Bouwhuis, J.W.; Barin, F.; Burty, C.; Duvivier, C.; Enel, P.; Fredouille-Heripret, L.; Gasnault, J.; Khuong, M.A.; Mahamat, A.; Pilorgé, F.; Tattevin, P.; Salomon, Valérie; Jacquemet, N.; Abgrall, S.; Costagliola, D.; Grabar, S.; Guiguet, M.; Lanoy, E.; Lièvre, L.; Mary-Krause, M.; Selinger-Leneman, H.; Lacombe, J.M.; Potard, V.; Bricaire, F.; Herson, S.; Katlama, C.; Simon, A.; Desplanque, N.; Girard, P.M.; Meynard, J.L.; Meyohas, M.C.; Picard, O.; Cadranel, J.; Mayaud, C.; Pialoux, G.; Clauvel, J.P.; Decazes, J.M.; Gerard, L.; Molina, J.M.; Diemer, M.; Sellier, P.; Bentata, M.; Honoré, P.; Jeantils, V.; Tassi, S.; Mechali, D.; Taverne, B.; Bouvet, E.; Crickx, B.; Ecobichon, J.L.; Matheron, S.; Picard-Dahan, C.; Yeni, P.; Berthé, H.; Dupont, C.; Chandemerle, C.; Mortier, E.; De Truchis, P.; Tisne-Dessus, D.; Weiss, L.; Salmon, D.; Auperin, I.; Gilquin, J.; Roudière, L.; Viard, J.P.; Boué, F.; Fior, R.; Delfraissy, J.F.; Goujard, C.; Jung, C.; Lesprit, Ph.; Vittecoq, D.; Fraisse, P.; Lang, J.M.; Rey, D.; Beck-Wirth, G.; Stahl, J.P.; Lecercq, P.; Gourdon, F.; Laurichesse, H.; Fresard, A.; Lucht, F.; Bazin, C.; Verdon, R.; Chavanet, P.; Arvieux, C.; Michelet, C.; Choutet, P.; Goudeau, A.; Maître, M.F.; Hoen, B.; Eglinger, P.; Faller, J.P.; Borsa-Lebas, F.; Caron, F.; Reynes, J.; Daures, J.P.; May, T.; Rabaud, C.; Berger, J.L.; Rémy, G.; Arlet-Suau, E.; Cuzin, L.; Massip, P.; Thiercelin Legrand, M.F.; Pontonnier, G.; Viget, N.; Yasdanpanah, Y.; Dellamonica, P.; Pradier, C.; Pugliese, P.; Aleksandrowicz, K.; Quinsat, D.; Ravaux, I.; Tissot-Dupont, H.; Delmont, J.P.; Moreau, J.; Gastaut, J.A.; Poizot-Martin, I.; Retornaz, F.; Soubeyrand, J.; Galinier, A.; Ruiz, J.M.; Allegre, T.; Blanc, P.A.; Bonnet-Montchardon, D.; Lepeu, G.; Granet-Brunello, P.; Esterni, J.P.; Pelissier, L.; Cohen-Valensi, R.; Nezri, M.; Chadapaud, S.; Laffeuillade, A.; Billaud, E.; Raffi, F.; Boibieux, A.; Peyramond, D.; Livrozet, J.M.; Touraine, J.L.; Cotte, L.; Trepo, C.; Strobel, M.; Bissuel, F.; Pradinaud, R.; Sobesky, M.; Cabié, A.; Gaud, C.; Contant, M.; Aubert, V.; Barth, J.; Battegay, M.; Bernasconi, E.; Böni, J.; Bucher, H.C.; Burton-Jeangros, C.; Calmy, A.; Cavassini, M.; Egger, M.; Elzi, L.; Fehr, J.; Fellay, J.; Furrer, H.; Haerry, D.; Fux, C.A.; Gorgievski, M.; Günthard, H.; Hasse, B.; Hirsch, H.H.; Hösli, I.; Kahlert, C.; Kaiser, L.; Keiser, O.; Klimkait, T.; Kovari, H.; Ledergerber, B.; Martinetti, G.; Martinez De Tejada, B.; Metzner, K.; Müller, N.; Nadal, D.; Pantaleo, G.; Rauch, A.; Regenass, S.; Rickenbach, M.; Rudin, C.; Schmid, P.; Schultze, D.; Schöni-Affolter, F.; Schüpbach, J.; Speck, R.; Taffé, P.; Tarr, P.; Telenti, A.; Trkola, A.; Vernazza, P.; Weber, R.; Yerly, S.; Casabona, J.; Gallois, A.; Esteve, A.; Podzamczer, D.; Murillas, J.; Gatell, J.M.; Manzardo, C.; Tural, C.; Clotet, B.; Ferrer, E.; Riera, M.; Segura, F.; Navarro, G.; Force, L.; Vilaró, J.; Masabeu, A.; García, I.; Guadarrama, M.; Cifuentes, C.; Dalmau, D.; Jaen, À.; Agustí, C.; Montoliu, A.; Pérez, I.; Gargoulas, Freyra; Blanco, J.L.; Garcia-Alcaide, F.; Martínez, E.; Mallolas, J.; López-Dieguez, M.; García-Goez, J.F.; Sirera, G.; Romeu, J.; Jou, A.; Negredo, E.; Miranda, C.; Capitan, M.C.; Saumoy, M.; Imaz, A.; Tiraboschi, J.M.; Murillo, O.; Bolao, F.; Peña, C.; Cabellos, C.; Masó, M.; Vila, A.; Sala, M.; Cervantes, M.; Jose Amengual, Ma.; Navarro, M.; Penelo, E.; Barrufet, P.; Bejarano, G.; Molina, J.; Guadarrama, M.; Alvaro, M.; Mercadal, J.; Fernandez, Juanse; Ospina, Jesus E.; Muñoz, M.A.; Caro-Murillo, A.M.; Sobrino, P.; Jarrín, I.; Gomez Sirvent, J.L.; Rodríguez, P.; Aleman, M.R.; Alonso, M.M.; Lopez, A.M.; Hernandez, M.I.; Soriano, V.; Labarga, P.; Barreiro, P.; Medrano, J.; Rivas, P.; Herrero, D.; Blanco, F.; Vispo, M.E.; Martín, L.; Ramírez, G.; De Diego, M.; Rubio, R.; Pulido, F.; Moreno, V.; Cepeda, C.; Hervás, Rl.; Iribarren, J.A.; Arrizabalaga, J.; Aramburu, M.J.; Camino, X.; Rodrí-guez-Arrondo, F.; Von Wichmann, M.A.; Pascual, L.; Goenaga, M.A.; Gutierrez, F.; Masia, M.; Ramos, J.M.; Padilla, S.; Sanchez-Hellín, V.; Bernal, E.; Escolano, C.; Montolio, F.; Peral, Y.; Berenguer, J.; Lopez, J.C.; Miralles, P.; Cosín, J.; Sanchez, M.; Gutierrez, I.; Ramírez, M.; Padilla, B.; Vidal, F.; Sanjuan, M.; Peraire, J.; Veloso, S.; Vilades, C.; Lopez-Dupla, M.; Olona, M.; Vargas, M.; Aldeguer, J.L.; Blanes, M.; Lacruz, J.; Salavert, M.; Montero, M.; Cuéllar, S.; De Los Santos, I.; Sanz, J.; Oteo, J.A.; Blanco, J.R.; Ibarra, V.; Metola, L.; Sanz, M.; Pérez-Martínez, L.; Sola, J.; Uriz, J.; Castiello, J.; Reparaz, J.; Arriaza, M.J.; Irigoyen, C.; Moreno, S.; Antela, A.; Casado, J.L.; Dronda, F.; Moreno, A.; Pérez, M.J.; López, D.; Gutiérrez, C.; Hernández, B.; Pumares, M.; Martí, P.; García, L.; Page, C.; García, F.; Hernández, J.; Peña, A.; Muñoz, L.; Parra, J.; Viciana, P.; Leal, M.; López-Cortés, L.F.; Trastoy, M.; Mata, R.; Justice, A.C.; Fiellin, D.A.; Rimland, D.; Jones-Taylor, C.; Oursler, K.A.; Titanji, R.; Brown, S.; Garrison, S.; Rodriguez-Barradas, M.; Masozera, N.; Goetz, M.; Leaf, D.; Simberkoff, M.; Blumenthal, D.; Leung, J.; Butt, A.; Hoffman, E.; Gibert, C.; Peck, R.; Mattocks, K.; Braithwaite, S.; Brandt, C.; Bryant, K.; Cook, R.; Conigliaro, J.; Crothers, K.; Chang, J.; Crystal, S.; Day, N.; Erdos, J.; Freiberg, M.; Kozal, M.; Gandhi, N.; Gaziano, M.; Gerschenson, M.; Good, B.; Gordon, A.; Goulet, J.L.; Hernán, M.A.; Kraemer, K.; Lim, J.; Maisto, S.; Miller, P.; Mole, L.; O'Connor, P.; Papas, R.; Robins, J.M.; Rinaldo, C.; Roberts, M.; Samet, J.; Tierney, B.; Whittle, J.; Babiker, A.; Brettle, R.; Darbyshire, J.; Gilson, R.; Goldberg, D.; Hawkins, D.; Jaffe, H.; Johnson, A.; McLean, K.; Pillay, D.; Cursley, Adam; Ewings, Fiona; Fairbrother, Keith; Louisa Gnatiuc, S.L.; Murphy, Brendan; Douglas, G.; Kennedy, N.; Pritchard, J.; Andrady, U.; Rajda, N.; Maw, R.; McKernan, S.; Drake, S.; Gilleran, G.; White, D.; Ross, J.; Toomer, S.; Hewart, R.; Wilding, H.; Woodward, R.; Dean, G.; Heald, L.; Horner, P.; Glover, S.; Bansaal, D.; Eduards, S.; Carne, C.; Browing, M.; Das, R.; Stanley, B.; Estreich, S.; Magdy, A.; O'Mahony, C.; Fraser, P.; Hayman, B.; Jebakumar, S.P.R.; Joshi, U.; Ralph, S.; Wade, A.; Mette, R.; Lalik, J.; Summerfield, H.; El-Dalil, A.; France, J.A.; White, C.; Robertson, R.; Gordon, S.; McMillan, S.; Morris, S.; Lean, C.; Vithayathil, K.; McLean, L.; Winter, A.; Gale, D.; Jacobs, S.; Tayal, S.; Short, L.; Roberts, M.; Green, S.; Williams, G.; Sivakumar, K.; Bhattacharyya, N.D.; Monteiro, E.; Minton, J.; Dhar, J.; Nye, F.; De Souza, C.B.; Isaksen, A.; McDonald, L.; McLean, K.; Franca, A.; Hawkins, D.; William, L.; Jendrulek, I.; Peters, B.; Shaunak, S.; El-Gadi, S.; Easterbrook, P.J.; Mazhude, C.; Gilson, R.; Johnstone, R.; Fakoya, A.; McHale, J.; Waters, A.; Kegg, S.; Mitchell, S.; Byrne, P.; Johnson, M.; Rice, P.; Fidler, S.; Mullaney, S.A.; McCormack, S.; David, D.; Melville, R.; Phillip, K.; Balachandran, T.; Mabey-Puttock, S.; Sukthankar, A.; Murphy, C.; Wilkins, E.; Ahmad, S.; Tayal, S.; Haynes, J.; Evans, E.; Ong, E.; Das, R.; Grey, R.; Meaden, J.; Bignell, C.; Loay, D.; Peacock, K.; Girgis, M.R.; Morgan, B.; Palfreeman, A.; Wilcox, J.; Tobin, J.; Tucker, L.; Saeed, A.M.; Chen, F.; Deheragada, A.; Williams, O.; Lacey, H.; Herman, S.; Kinghorn, D.; Devendra, V.S.; Wither, J.; Dawson, S.; Rowen, D.; Harvey, J.; Wilkins, E.; Bridgwood, A.; Singh, G.; Chauhan, M.; Kellock, D.; Young, S.; Dannino, S.; Kathir, Y.; Rooney, G.; Currie, J.; Fitzgerald, M.; Devendra, S.; Keane, F.; Booth, G.; Green, T.; Arumainayyagam, J.; Chandramani, S.; Rajamanoharan, S.; Robinson, T.; Curless, E.; Gokhale, R.; Tariq, A.; Roberts, M.; Williams, O.; Luzzi, G.; FitzGerald, M.; Fairley, I.; Wallis, F.; Smit, E.; Ward, F.; Molina, J.M.; Loze, B.; Morlat, P.; Bonarek, M.; Bonnet, F.; Nouts, C.; Louis, I.; Raffi, F.; Reliquet, V.; Sauser, F.; Biron, C.; Mounoury, O.; Hue, H.; Brosseau, D.; Delfraissy, J.F.; Goujard, C.; Ghosn, J.; Rannou, M.T.; Bergmann, J.F.; Badsi, E.; Rami, A.; Diemer, M.; Parrinello, M.; Girard, P.M.; Samanon-Bollens, D.; Campa, P.; Tourneur, M.; Desplanques, N.; Livrozet, J.M.; Jeanblanc, F.; Chiarello, P.; Makhloufi, D.; Blanc, A.P.; Allègre, T.; Reynes, J.; Baillat, V.; Lemoing, V.; Merle De Boever, C.; Tramoni, C.; Cabié, A.; Sobesky, G.; Abel, S.; Beaujolais, V.; Pialoux, G.; Slama, L.; Chakvetadze, C.; Berrebi, V.; Yeni, P.; Bouvet, E.; Fournier, I.; Gerbe, J.; Trepo, C.; Koffi, K.; Augustin-Normand, C.; Miailhes, P.; Thoirain, V.; Brochier, C.; Thomas, R.; Souala, F.; Ratajczak, M.; Beytoux, J.; Jacomet, C.; Gourdon, F.; Rouveix, E.; Morelon, S.; Dupont, C.; Olivier, C.; Lortholary, O.; Dupont, B.; Viard, J.P.; Maignan, A.; Ragnaud, J.M.; Raymond, I.; Leport, C.; Jadand, C.; Jestin, C.; Longuet, P.; Boucherit, S.; Sereni, D.; Lascoux, C.; Prevoteau, F.; Sobel, A.; Levy, Y.; Lelièvre, J.D.; Lascaux, A.S.; Dominguez, S.; Dumont, C.; Aumâitre, H.; Delmas, B.; Saada, M.; Medus, M.; Guillevin, L.; Salmon, D.; Tahi, T.; Yazdanpanah, Y.; Pavel, S.; Marien, M.C.; Drenou, B.; Beck-Wirth, G.; Beck, C.; Benomar, M.; Katlama, C.; Tubiana, R.; Ait Mohand, H.; Chermak, A.; Ben Abdallah, S.; Bentata, M.; Touam, F.; Hoen, B.; Drobacheff, C.; Folzer, A.; Massip, P.; Obadia, M.; Prudhomme, L.; Bonnet, E.; Balzarin, F.; Pichard, E.; Chennebault, J.M.; Fialaire, P.; Loison, J.; Galanaud, P.; Boué, F.; Bornarel, D.; Verdon, R.; Bazin, C.; Six, M.; Ferret, P.; Weiss, L.; Batisse, D.; Gonzales-Canali, G.; Tisne-Dessus, D.; Devidas, A.; Chevojon, P.; Turpault, I.; Lafeuillade, A.; Cheret, A.; Philip, G.; Morel, P.; Timsit, J.; Herson, S.; Amirat, N.; Simon, A.; Brancion, C.; Cabane, J.; Picard, O.; Tredup, J.; Stein, A.; Ravault, I.; Chavanet, C.; Buisson, M.; Treuvetot, S.; Choutet, P.; Nau, P.; Bastides, F.; May, T.; Boyer, L.; Wassoumbou, S.; Oksenhendeler, E.; Gérard, L.; Bernard, L.; De Truchis, P.; Berthé, H.; Domart, Y.; Merrien, D.; Greder Belan, A.; Gayraud, M.; Bodard, L.; Meudec, A.; Beuscart, C.; Daniel, C.; Pape, E.; Vinceneux, P.; Simonpoli, A.M.; Zeng, A.; Fournier, L.; Fuzibet, J.G.; Sohn, C.; Rosenthal, E.; Quaranta, M.; Dellamonica, P.; Chaillou, S.; Sabah, M.; Audhuy, B.; Schieber, A.; Moreau, P.; Niault, M.; Vaillant, O.; Huchon, G.; Compagnucci, A.; De Lacroix Szmania, I.; Richier, L.; Lamaury, I.; Saint-Dizier, F.; Garipuy, D.; Gastaut, J.A.; Drogoul, M.P.; Poizot Martin, I.; Fabre, G.; Lambert De Cursay, G.; Abraham, B.; Perino, C.; Lagarde, P.; David, F.; Roche-Sicot, J.; Saraux, J.L.; Leprêtre, A.; Fampin, B.; Uludag, A.; Morin, A.S.; Bletry, O.; Zucman, D.; Regnier, A.; Girard, J.J.; Quinsat, D.T.; Heripret, L.; Grihon, F.; Houlbert, D.; Ruel, M.; Chemlal, K.; Caron, F.; Debab, Y.; Tremollieres, F.; Perronne, V.; Lepeu, G.; Slama, B.; Perré, P.; Miodovski, C.; Guermonprez, G.; Dulioust, A.; Boudon, P.; Malbec, D.; Patey, O.; Semaille, C.; Deville, J.; Remy, G.; Béguinot, I.; Galanaud, P.; Boue, F.; Chambrin, V.; Pignon, C.; Estocq, G.A.; Levy, A.; Delfraissy, J.F.; Goujard, C.; Duracinsky, M.; Le Bras, P.; Ngussan, M.S.; Peretti, D.; Medintzeff, N.; Lambert, T.; Segeral, O.; Lezeau, P.; Laurian, Y.; Weiss, L.; Buisson, M.; Piketty, C.; Karmochkine, M.; Batisse, D.; Eliaszewitch, M.; Jayle, D.; Tisne-Dessus, D.; Kazatchkine, M.; Leport, C.; Colasante, U.; Jadand, C.; Jestin, C.; Duval, X.; Nouaouia, W.; Boucherit, S.; Vilde, J.L.; Girard, P.M.; Bollens, D.; Binet, D.; Diallo, B.; Meyohas, M.C.; Fonquernie, L.; Lagneau, J.L.; Salmon, D.; Guillevin, L.; Tahi, T.; Launay, O.; Pietrie, M.P.; Sicard, D.; Stieltjes, N.; Michot, J.; Sobel, A.; Levy, Y.; Bourdillon, F.; Lascaux, A.S.; Lelievre, J.D.; Dumont, C.; Dupont, B.; Obenga, G.; Viard, J.P.; Maignan, A.; Vittecoq, D.; Escaut, L.; Bolliot, C.; Bricaire, F.; Katlama, C.; Schneider, L.; Herson, S.; Simon, A.; Iguertsira, M.; Stein, A.; Tomei, C.; Ravaux, I.; Dhiver, C.; Tissot Dupont, H.; Vallon, A.; Gallais, J.; Gallais, H.; Gastaut, J.A.; Drogoul, M.P.; Fabre, G.; Dellamonica, P.; Durant, J.; Mondain, V.; Perbost, I.; Cassuto, J.P.; Karsenti, J.M.; Venti, H.; Fuzibet, J.G.; Rosenthal, E.; Ceppi, C.; Quaranta, M.; Krivitsky, J.A.; Bentata, M.; Bouchaud, O.; Honore, P.; Sereni, D.; Lascoux, C.; Delgado, J.; Rouzioux, C.; Burgard, M.; Boufassa, L.; Peynet, J.; Pérez-Hoyos, S.; Del Amo, J.; Alvarez, D.; Monge, S.; Muga, R.; Sanvisens, A.; Clotet, B.; Tor, J.; Bolao, F.; Rivas, I.; Vallecillo, G.; Del Romero, J.; Raposo, P.; Rodríguez, C.; Vera, M.; Hurtado, I.; Belda, J.; Fernandez, E.; Alastrue, I.; Santos, C.; Tasa, T.; Juan, A.; Trullen, J.; Garcia De Olalla, P.; Cayla, J.; Masdeu, E.; Knobel, H.; Mirò, J.M.; Sambeat, M.A.; Guerrero, R.; Rivera, E.; Guerrero, R.; Marco, A.; Quintana, M.; Gonzalez, C.; Castilla, J.; Guevara, M.; De Mendoza, C.; Zahonero, N.; Ortíz, M.; Paraskevis, D.; Touloumi, G.; Pantazis, N.; Bakoyannis, G.; Gioukari, V.; Antoniadou, A.; Papadopoulos, A.; Petrikkos, G.; Daikos, G.; Psichogiou, M.; Gargalianos-Kakolyris, P.; Xylomenos, G.; Katsarou, O.; Kouramba, A.; Ioannidou, P.; Kordossis, T.; Kontos, A.; Lazanas, M.; Chini, M.; Tsogas, N.; Panos, G.; Paparizos, V.; Leuow, K.; Kourkounti, S.; Sambatakou, H.; Mariolis, I.; Skoutelis, A.; Papastamopoulos, V.; Baraboutis, I.

    2014-01-01

    Background: There is little information on the incidence of AIDS-defining events which have been reported in the literature to be associated with immune reconstitution inflammatory syndrome (IRIS) after combined antiretroviral therapy (cART) initiation. These events include tuberculosis,

  13. Strategies for combinational cancer therapies

    International Nuclear Information System (INIS)

    Khleif, Samir

    2014-01-01

    The countless pre-clinical studies and many clinical trials that have applied tumor antigen-based therapies for the cancer treatment, and although the necessary tumor-specific immune response may be elicited in tumor-bearing hosts, this was not sufficient for the positive therapeutic outcome since there are multiple mechanisms that tumors develop to escape immune surveillance. The tumor-mediated inhibitory mechanisms involve co-inhibitory receptor-ligand interactions, such as PD-1/ PD-L1, secretion of inhibitory molecules, such as TGFb, and recruitment of suppressive cells, such as regulatory T cells (Treg), myeloid derived suppressor cells (MDSC), etc. Therefore, we hypothesized that successful cancer immunotherapy requires not only induction and enhancement of effector immune response but also simultaneous targeting of suppressor arm of immune system, thus in addition to enhancing antigen-specific immunity using vaccines or radiation therapy, one should also target tumor-mediated immune suppression to improve the overall efficacy of therapy. We developed multiple strategies to target various tumor-mediated immune inhibitory mechanisms that can enhance anti-tumor immunity and restructure tumor microenvironment to allow effector cells generated due to vaccination or radiation therapy to function potently. We evaluated the immune and therapeutic efficacy of multiple combinational therapies, including blocking and agonist antibodies to co-inhibitory/co-stimulatory molecules, such as PD-1, PD-L1, OX40, CTLA-4, GITR, inhibitors and neutralizing antibodies to inhibitory cytokines/molecules, such as IL-10, TGFb, IDO, and small molecules for selective inhibition of Tregs. In addition to evaluation of anti-tumor efficacy we are also investigated cellular and molecular mechanisms of action for these agents when combined with vaccine or radiation therapy and exploring the interactions between compounds within combinational therapies in animal tumor models. We are

  14. Therapy of infections in mice irradiated in mixed neutron/photon fields and inflicted with wound trauma: a review of current work.

    Science.gov (United States)

    Ledney, G D; Madonna, G S; Elliott, T B; Moore, M M; Jackson, W E

    1991-10-01

    When host antimicrobial defenses are severely compromised by radiation or trauma in conjunction with radiation, death from sepsis results. To evaluate therapies for sepsis in radiation casualties, we developed models of acquired and induced bacterial infections in irradiated and irradiated-wounded mice. Animals were exposed to either a mixed radiation field of equal proportions of neutrons and gamma rays (n/gamma = 1) from a TRIGA reactor or pure gamma rays from 60[Co sources. Skin wounds (15% of total body surface area) were inflicted under methoxyflurane anesthesia 1 h after irradiation. In all mice, wounding after irradiation decreased resistance to infection. Treatments with the immunomodulator synthetic trehalose dicorynomycolate (S-TDCM) before or after mixed neutron-gamma irradiation or gamma irradiation increased survival. Therapy with S-TDCM for mice irradiated with either a mixed field or gamma rays increased resistance to Klebsiella pneumoniae-induced infections. Combined therapy with S-TDCM and ceftriaxone for K. pneumoniae infections in mice exposed to a mixed radiation field or to gamma rays was more effective than single-agent therapy. In all irradiated-wounded mice, single therapy of acquired infections with an antibiotic or S-TDCM did not increase survival. Survival of irradiated-wounded mice after topical application of gentamicin sulfate cream suggested that bacteria colonizing the wound disseminated systemically in untreated irradiated mice, resulting in death from sepsis. In lethal models of acquired infections in irradiated-wounded mice, significant increases in survival were achieved when systemic treatments with S-TDCM or gentamicin were combined with topical treatments of gentamicin cream. Therapies for sepsis in all mice exposed to a mixed field were less effective than in mice exposed to gamma rays. Nonetheless, the data show a principle by which successful therapy may be provided to individuals receiving tissue trauma in conjunction with

  15. Options for empagliflozin in combination therapy in type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Hershon KS

    2016-05-01

    Full Text Available Kenneth S Hershon1,2 1North Shore Diabetes and Endocrine Associates, New Hyde Park, 2Department of Medicine, Hofstra Northwell School of Medicine, Hempstead, NY, USA Objective: To update clinicians with an overview of empagliflozin for the treatment of type 2 diabetes mellitus (T2DM, with focus on use in combination regimens. Methods: Keyword searches were conducted in the Medline database to identify literature reporting clinical trials of at least 12 weeks' duration using empagliflozin treatment in patients with T2DM. Results: When given as monotherapy or in combination therapy (as add-on or single-pill therapy with metformin, pioglitazone, sulfonylurea, linagliptin, and insulin, empagliflozin produced clinically meaningful reductions in glycated hemoglobin levels, plasma glucose concentrations, bodyweight, and blood pressure. These changes were sustained during long-term treatment. In a dedicated cardiovascular event trial, empagliflozin on top of standard of care demonstrated a significant reduction in the risk of cardiovascular mortality and all-cause mortality. Across the clinical trials, empagliflozin combination therapies were well tolerated, and empagliflozin used alone was not associated with increased risk of hypoglycemia versus placebo. Indeed, the combination of empagliflozin and metformin had a significantly reduced rate of hypoglycemia compared with the combination of metformin and a sulfonylurea. On the other hand, empagliflozin treatment did have increased risk of genital infections compared with placebo. In clinical trials to date, diabetic ketoacidosis was not seen more frequently with empagliflozin than with placebo, but physicians should be alert to the possibility of this rare event. Conclusion: Empagliflozin has the potential to make an important contribution to the treatment of patients with T2DM. In some patients, empagliflozin may be used as monotherapy, but it is most likely to be used in combination with other

  16. Effectiveness of Combination Therapy with Honey in H.Pylori Eradication in Pediatrics Medical Centre

    Directory of Open Access Journals (Sweden)

    Z.N. Hatmi

    2006-07-01

    Full Text Available Background: There are several million new cases of peptic disease annually. The disease has a various range of presentations. Gram negative helicobacter pylori bacilli is considered as an etiologic factor in this disease. Goal of treatment in peptic disease is eradication of the helicobacter pylori (HP. Combination therapy has been implemented in the treatment of this disease. Different modalities have been recommended up to now. In order to lower adverse effects, cost and drug resistance, researchers have introduced a new combination therapy in which honey is substituted for metronidazole. Methods: A step II of clinical trial was designed. The sample size was 15 children. Diagnosis of HP infection was confirmed with histopathology. Treatment regimen consisted of omeprazole, amoxicillin, bismuth and honey. After a 3-4 week follow- up, eradication was evaluated. Results: 15 children completed the follow- up period. Mean age of patients was 9.4 years. Treatment effectiveness was 80 percent. Conclusion: Combination therapy with 3 drugs along with honey has significant effectiveness on HP eradication.

  17. Interleukin-2 therapy in patients with HIV infection.

    Science.gov (United States)

    Abrams, D; Lévy, Y; Losso, M H; Babiker, A; Collins, G; Cooper, D A; Darbyshire, J; Emery, S; Fox, L; Gordin, F; Lane, H C; Lundgren, J D; Mitsuyasu, R; Neaton, J D; Phillips, A; Routy, J P; Tambussi, G; Wentworth, D

    2009-10-15

    Used in combination with antiretroviral therapy, subcutaneous recombinant interleukin-2 raises CD4+ cell counts more than does antiretroviral therapy alone. The clinical implication of these increases is not known. We conducted two trials: the Subcutaneous Recombinant, Human Interleukin-2 in HIV-Infected Patients with Low CD4+ Counts under Active Antiretroviral Therapy (SILCAAT) study and the Evaluation of Subcutaneous Proleukin in a Randomized International Trial (ESPRIT). In each, patients infected with the human immunodeficiency virus (HIV) who had CD4+ cell counts of either 50 to 299 per cubic millimeter (SILCAAT) or 300 or more per cubic millimeter (ESPRIT) were randomly assigned to receive interleukin-2 plus antiretroviral therapy or antiretroviral therapy alone. The interleukin-2 regimen consisted of cycles of 5 consecutive days each, administered at 8-week intervals. The SILCAAT study involved six cycles and a dose of 4.5 million IU of interleukin-2 twice daily; ESPRIT involved three cycles and a dose of 7.5 million IU twice daily. Additional cycles were recommended to maintain the CD4+ cell count above predefined target levels. The primary end point of both studies was opportunistic disease or death from any cause. In the SILCAAT study, 1695 patients (849 receiving interleukin-2 plus antiretroviral therapy and 846 receiving antiretroviral therapy alone) who had a median CD4+ cell count of 202 cells per cubic millimeter were enrolled; in ESPRIT, 4111 patients (2071 receiving interleukin-2 plus antiretroviral therapy and 2040 receiving antiretroviral therapy alone) who had a median CD4+ cell count of 457 cells per cubic millimeter were enrolled. Over a median follow-up period of 7 to 8 years, the CD4+ cell count was higher in the interleukin-2 group than in the group receiving antiretroviral therapy alone--by 53 and 159 cells per cubic millimeter, on average, in the SILCAAT study and ESPRIT, respectively. Hazard ratios for opportunistic disease or death from

  18. Lamivudine plus adefovir combination therapy versus entecavir monotherapy for lamivudine-resistant chronic hepatitis B: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Hu Peng

    2011-08-01

    Full Text Available Abstract Background Chronic hepatitis B virus (HBV infection represents a serious global health problem and resistance to lamivudine (LAM has become a serious clinical challenge. Previous rescue therapy for the treatment of chronic LAM-resistant hepatitis B infected patients included switching to entecavir (ETV and adding adefovir (ADV or tenofovir (TFV. At present, switching to ETV is not recommended for rescue therapy for LAM-resistant chronic hepatitis B (CHB. The aim of this report was to determine whether add-on ADV was a superior rescue strategy in the treatment of CHB patients with LAM resistance. Methods We searched Medline/PubMed, EMBASE, Web of Knowledge, and the Cochrane Library. Relative risks (RRs of virologic response, virologic breakthrough, normalization of serum alanine aminotransferase (ALT levels and HBeAg seroconversion rates were studied. Factors predicting virologic response, standardized mean differences (SMD in HBV DNA levels and safety were reviewed. Results Six eligible trials (451 patients in total were included in the analysis. The rate of virologic breakthrough in the ETV group was higher than that in the LAM plus ADV group. There were no statistical differences in virologic response, ALT normalization and HBeAg seroconversion in either group 48 weeks post treatment. LAM plus ADV combination therapy produced faster and greater HBV DNA reduction rates 24 weeks post therapy compared to ETV monotherapy. HBV DNA baseline levels and the initial virologic response (IVR were predictive of the virologic response. Additionally, combination therapy or monotherapy were both well tolerated. Conclusions LAM plus ADV combination therapy was more effective and produced longer-lasting effects than switching to ETV monotherapy in treating CHB patients with LAM resistance. However, considering the practical benefits and limitations of ADV, individualized therapy will be needed in patients with prior history of LAM resistant infections.

  19. Infection After Hysterectomy

    Directory of Open Access Journals (Sweden)

    David L. Hemsell

    1997-01-01

    Full Text Available Antibiotic prophylaxis and advances in technology have reduced operative site infections after hysterectomy to a minimum. Pelvic infections are the most common infection type and respond promptly to a variety of parenteral single-agent and combination antibiotic regimens. Oral antibiotic regimens following parenteral therapy are unnecessary. Abdominal incision infections are less common than pelvic infections, less common than seromas or hematomas, and usually do not require antimicrobial therapy. Abscesses or infected hematomas require parenteral antimicrobial therapy, and drainage of those located above the cuff will predictably shorten therapy time. With early discharge from the hospital, many infections will not become evident until after the patient is home. For that reason, it is important that the patient's discharge instructions outline symptoms and signs associated with these infections so she can present for care at the earliest possible time.

  20. History of viral suppression on combination antiretroviral therapy as a predictor of virological failure after a treatment change

    DEFF Research Database (Denmark)

    Reekie, J; Mocroft, A; Ledergerber, B

    2010-01-01

    OBJECTIVES: HIV-infected persons experience different patterns of viral suppression after initiating combination antiretroviral therapy (cART). The relationship between such differences and risk of virological failure after starting a new antiretroviral could help with patient monitoring strategi...

  1. Efficacy of ciprofloxacin-gentamicin combination therapy in murine bubonic plague.

    Directory of Open Access Journals (Sweden)

    Nadine Lemaître

    Full Text Available Potential benefits of combination antibiotic therapy for the treatment of plague have never been evaluated. We compared the efficacy of a ciprofloxacin (CIN and gentamicin (GEN combination therapy with that of each antibiotic administered alone (i against Yersinia pestis in vitro and (ii in a mouse model of bubonic plague in which animals were intravenously injected with antibiotics for five days, starting at two different times after infection (44 h and 56 h. In vitro, the CIN+GEN combination was synergistic at 0.5x the individual drugs' MICs and indifferent at 1x- or 2x MIC. In vivo, the survival rate for mice treated with CIN+GEN was similar to that observed with CIN alone and slightly higher than that observed for GEN alone 100, 100 and 85%, respectively when treatment was started 44 h post challenge. 100% of survivors were recorded in the CIN+GEN group vs 86 and 83% in the CIN and GEN groups, respectively when treatment was delayed to 56 h post-challenge. However, these differences were not statistically significant. Five days after the end of treatment, Y. pestis were observed in lymph nodes draining the inoculation site (but not in the spleen in surviving mice in each of the three groups. The median lymph node log(10 CFU recovered from persistently infected lymph nodes was significantly higher with GEN than with CIN (5.8 vs. 3.2, p = 0.04 or CIN+GEN (5.8 vs. 2.8, p = 0.01. Taken as the whole, our data show that CIN+GEN combination is as effective as CIN alone but, regimens containing CIN are more effective to eradicate Y. pestis from the draining lymph node than the recommended GEN monotherapy. Moreover, draining lymph nodes may serve as a reservoir for the continued release of Y. pestis into the blood - even after five days of intravenous antibiotic treatment.

  2. Optimizing empiric therapy for Gram-negative bloodstream infections in children.

    Science.gov (United States)

    Chao, Y; Reuter, C; Kociolek, L K; Patel, R; Zheng, X; Patel, S J

    2018-06-01

    Antimicrobial stewardship can be challenging in children with bloodstream infections (BSIs) caused by Gram-negative bacilli (GNB). This retrospective cohort study explored how data elements in the electronic health record could potentially optimize empiric antibiotic therapy for BSIs caused by GNB, via the construction of customized antibiograms for categorical GNB infections and identification of opportunities to minimize organism-drug mismatch and decrease time to effective therapy. Our results suggest potential strategies that could be implemented at key decision points in prescribing at initiation, modification, and targeting of therapy. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  3. EPIDEMIOLOGICAL AND CLINICAL FEATURES OF COMBINED RESPIRATORY INFECTIONS IN CHILDREN

    Directory of Open Access Journals (Sweden)

    V. V. Shkarin

    2017-01-01

    Full Text Available Presents a review of publications on the problem of combined respiratory infections among children. Viral-bacterial associations are registered  in a group of often ill children in 51.7%. More than half of the patients have herpesvirus infection in various combinations. The presence of a combined acute respiratory viral infection among children in the group from 2 to 6 years was noted in 44.2% of cases, among which, in addition to influenza viruses, RS-, adeno-, etc., metapneumovirus and bocavirus plays an important role.The increase in severity of acute respiratory viral infection with combined  infection, with chlamydia  and mycoplasma infection is shown. A longer and more severe course of whooping cough was observed when combined with respiratory viruses.The revealed facts of frequency of distribution of combined  respiratory infections in children, the severity and duration of their course with the development of various complications and the formation of chronic pathology dictate the need to improve diagnosis and treatment tactics of these forms of infections.

  4. Combination therapy in type 2 diabetes mellitus: adding empagliflozin to basal insulin

    Directory of Open Access Journals (Sweden)

    Andrew Ahmann

    2015-11-01

    Full Text Available Type 2 diabetes mellitus (T2DM management is complex, with few patients successfully achieving recommended glycemic targets with monotherapy, most progressing to combination therapy, and many eventually requiring insulin. Sodium glucose cotransporter 2 (SGLT2 inhibitors are an emerging class of antidiabetes agents with an insulin-independent mechanism of action, making them suitable for use in combination with any other class of antidiabetes agents, including insulin. This review evaluates a 78-week, randomized, double-blind, placebo-controlled trial investigating the impact of empagliflozin, an SGLT2 inhibitor, as add-on to basal insulin in patients with inadequate glycemic control on basal insulin, with or without metformin and/or a sulfonylurea. Empagliflozin added on to basal insulin resulted in significant and sustained reductions in glycated hemoglobin (HbA1c levels compared with placebo. Empagliflozin has previously been shown to induce weight loss, and was associated with sustained weight loss in this study. This combination therapy was well tolerated, with similar levels of hypoglycemic adverse events in the empagliflozin and placebo groups over the 78-week treatment period. Urinary tract infections and genital infections, side effects associated with SGLT2 inhibitors, were reported more commonly in the empagliflozin group; however, such events led to treatment discontinuation in very few patients. These findings suggest that, with their complementary mechanisms of action, empagliflozin added on to basal insulin may be a useful treatment option in patients on basal insulin who need additional glycemic control without weight gain.

  5. Candida Infective Endocarditis: an Observational Cohort Study with a Focus on Therapy

    Science.gov (United States)

    Johnson, Melissa; Bayer, Arnold S.; Bradley, Suzanne; Giannitsioti, Efthymia; Miró, José M.; Tornos, Pilar; Tattevin, Pierre; Strahilevitz, Jacob; Spelman, Denis; Athan, Eugene; Nacinovich, Francisco; Fortes, Claudio Q.; Lamas, Cristiane; Barsic, Bruno; Fernández-Hidalgo, Nuria; Muñoz, Patricia; Chu, Vivian H.

    2015-01-01

    Candida infective endocarditis is a rare disease with a high mortality rate. Our understanding of this infection is derived from case series, case reports, and small prospective cohorts. The purpose of this study was to evaluate the clinical features and use of different antifungal treatment regimens for Candida infective endocarditis. This prospective cohort study was based on 70 cases of Candida infective endocarditis from the International Collaboration on Endocarditis (ICE)-Prospective Cohort Study and ICE-Plus databases collected between 2000 and 2010. The majority of infections were acquired nosocomially (67%). Congestive heart failure (24%), prosthetic heart valve (46%), and previous infective endocarditis (26%) were common comorbidities. Overall mortality was high, with 36% mortality in the hospital and 59% at 1 year. On univariate analysis, older age, heart failure at baseline, persistent candidemia, nosocomial acquisition, heart failure as a complication, and intracardiac abscess were associated with higher mortality. Mortality was not affected by use of surgical therapy or choice of antifungal agent. A subgroup analysis was performed on 33 patients for whom specific antifungal therapy information was available. In this subgroup, 11 patients received amphotericin B-based therapy and 14 received echinocandin-based therapy. Despite a higher percentage of older patients and nosocomial infection in the echinocandin group, mortality rates were similar between the two groups. In conclusion, Candida infective endocarditis is associated with a high mortality rate that was not impacted by choice of antifungal therapy or by adjunctive surgical intervention. Additionally, echinocandin therapy was as effective as amphotericin B-based therapy in the small subgroup analysis. PMID:25645855

  6. [Immunomodulators in Therapy of Respiratory Infections].

    Science.gov (United States)

    Isakov, V A; Isakov, D V

    2014-01-01

    Viral infections provoke dysbalance in the interferon system and inhibition of the cellular and phagocytic responses of the host. Long-term persistence of pathogenic viruses and bacteria induce atopy and could aggravate chronic respiratory diseases. The up-to-date classification of immunomodulators is described. High efficacy of interferon inductors, such as cycloferon and some others as auxiliary means in therapy or prophylaxis (immunorehabilitation) of viral respiratory infections in adults and children was shown.

  7. Lactobacillus reuteri strain combination in Helicobacter pylori infection: a randomized, double-blind, placebo-controlled study.

    Science.gov (United States)

    Francavilla, Ruggiero; Polimeno, Lorenzo; Demichina, Antonella; Maurogiovanni, Giovanni; Principi, Beatrice; Scaccianoce, Giuseppe; Ierardi, Enzo; Russo, Francesco; Riezzo, Giuseppe; Di Leo, Alfredo; Cavallo, Luciano; Francavilla, Antonio; Versalovic, James

    2014-01-01

    The goals of this study were to investigate the role of a new probiotic preparation (Lactobacillus reuteri DSM 17938 and L. reuteri ATCC PTA 6475) in Helicobacter pylori infection. Specific probiotic strains play a role in H. pylori infection for their ability to decrease bacterial load and gastritis, prevent antibiotic-associated side effects, and increase the eradication rate. This is a prospective, double-blind, randomized, placebo-controlled study in a tertiary care setting. A total of 100 H. pylori-positive naive patients received either L. reuteri combination (2×10 Colony Forming Units) or placebo during a 3-phase study (pre-eradication, eradication, and follow-up). All underwent C urea breath test (C-UBT), blood assessments of gastrin-17 (G17), endoscopy, and the Gastrointestinal Symptom Rating Scale. Eradication was confirmed by C-UBT 8 weeks after the completion of therapy. Fifty patients were allocated in each group. During pre-eradication period, C-UBT δ decreased by 13% in L. reuteri combination as compared with a 4% increase in placebo (-13.2±34% vs. 4.3±27%; Preuteri combination (6.8±2.9 vs. 4±3.1; Preuteri combination as compared with placebo-reported side effects (40.9% vs. 62.8%; Preuteri combination (28% vs. 12%; Preuteri combination and 65.9% in placebo (P=NS). L. reuteri combination increased eradication rate by 9.1% (odds ratio: 1.5). L. reuteri combination alone is able to exert an inhibitory effect on H. pylori growth, and when administered with eradication therapy, it determines a significant reduction in antibiotic-associated side effects. Moreover, L. reuteri combination was able to decrease serum G17 levels and to (not significantly) increase the H. pylori-eradication rate.

  8. Can vacuum-assisted closure and instillation therapy (VAC-Instill therapy) play a role in the treatment of the infected open abdomen?

    Science.gov (United States)

    D'Hondt, M; D'Haeninck, A; Dedrye, L; Penninckx, F; Aerts, R

    2011-03-01

    Severe superimposed infection during open abdomen treatment with development of intra-abdominal sepsis is a challenging complication associated with high mortality rates. We report our experience with VAC-Instill therapy (KCI, San Antonio, USA) used for treatment of an infected open abdomen following pancreatic surgery. A literature search revealed no analogous case reports using VAC-Instill therapy for treatment of an infected laparostomy. The encouraging result of the case presented seems to indicate that VAC-Instill therapy could be used as adjunctive treatment in the management of the infected open abdomen when traditional therapy fails to control the infection.

  9. Candida infective endocarditis: an observational cohort study with a focus on therapy.

    Science.gov (United States)

    Arnold, Christopher J; Johnson, Melissa; Bayer, Arnold S; Bradley, Suzanne; Giannitsioti, Efthymia; Miró, José M; Tornos, Pilar; Tattevin, Pierre; Strahilevitz, Jacob; Spelman, Denis; Athan, Eugene; Nacinovich, Francisco; Fortes, Claudio Q; Lamas, Cristiane; Barsic, Bruno; Fernández-Hidalgo, Nuria; Muñoz, Patricia; Chu, Vivian H

    2015-04-01

    Candida infective endocarditis is a rare disease with a high mortality rate. Our understanding of this infection is derived from case series, case reports, and small prospective cohorts. The purpose of this study was to evaluate the clinical features and use of different antifungal treatment regimens for Candida infective endocarditis. This prospective cohort study was based on 70 cases of Candida infective endocarditis from the International Collaboration on Endocarditis (ICE)-Prospective Cohort Study and ICE-Plus databases collected between 2000 and 2010. The majority of infections were acquired nosocomially (67%). Congestive heart failure (24%), prosthetic heart valve (46%), and previous infective endocarditis (26%) were common comorbidities. Overall mortality was high, with 36% mortality in the hospital and 59% at 1 year. On univariate analysis, older age, heart failure at baseline, persistent candidemia, nosocomial acquisition, heart failure as a complication, and intracardiac abscess were associated with higher mortality. Mortality was not affected by use of surgical therapy or choice of antifungal agent. A subgroup analysis was performed on 33 patients for whom specific antifungal therapy information was available. In this subgroup, 11 patients received amphotericin B-based therapy and 14 received echinocandin-based therapy. Despite a higher percentage of older patients and nosocomial infection in the echinocandin group, mortality rates were similar between the two groups. In conclusion, Candida infective endocarditis is associated with a high mortality rate that was not impacted by choice of antifungal therapy or by adjunctive surgical intervention. Additionally, echinocandin therapy was as effective as amphotericin B-based therapy in the small subgroup analysis. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  10. Mycobacterium avium Infection after Acupoint Embedding Therapy

    Directory of Open Access Journals (Sweden)

    Jiao Zhang, MD

    2017-09-01

    Full Text Available Summary:. Nontuberculous mycobacterium is a ubiquitous environmental organism that is unusual to cause a true infection, but it can cause severe cutaneous infections. In this case report, we present a successful treatment for a Chinese patient with Mycobacterium avium cutaneous infection after acupoint embedding therapy. We managed to conduct pathogenic detection, drug sensitive test, and multidisciplinary consultation. Finally, a systematic treatment strategy of nontuberculous mycobacterium was performed. Twenty-two-month follow-up revealed excellent outcome without any recurrence.

  11. Safety of Sofosbuvir and Ribavirin Combination Therapy in a Patient Who Developed Anemia due to Ribavirin

    Directory of Open Access Journals (Sweden)

    Hirokazu Suii

    2017-01-01

    Full Text Available Interferon (IFN and ribavirin (RBV combination therapy was previously the standard of care for treatment of hepatitis C virus (HCV genotype 2 infection. But, it often induced hemolytic anemia. In 2014, sofosbuvir (SOF was approved for the treatment of chronic HCV genotype 2 in Japan. SOF/RBV therapy is more effective against genotype 2 than IFN/RBV therapy. We report a case of a 74-year-old woman with chronic HCV genotype 2b infection. She received five treatments including RBV and IFN therapy before SOF was approved and all of them were ineffective. Therapies that included RBV induced severe anemia and led to discontinuation of treatment. With pegylated IFN/RBV therapy, the maximum change in hemoglobin (Hb from baseline was −3.7 g/dL. However, SOF/RBV therapy was effective and she achieved sustained virologic response (SVR with a maximum change in Hb from baseline of only −1.2 g/dL. We also found reticulocyte count was very low during treatment in this case and speculate it was one of the reasons that she developed hemolytic anemia with RBV. In conclusion, SOF/RBV therapy is effective and allowed the patient to achieve SVR. An SOF/RBV regimen is safe and effective for patients who have or are at risk of anemia induced by RBV.

  12. CURCUMIN IN COMBINATION WITH TRIPLE THERAPY REGIMES AMELIORATES OXIDATIVE STRESS AND HISTOPATHOLOGIC CHANGES IN CHRONIC GASTRITIS-ASSOCIATED HELICOBACTER PYLORI INFECTION.

    Science.gov (United States)

    Judaki, Arezu; Rahmani, Asghar; Feizi, Jalil; Asadollahi, Khairollah; Hafezi Ahmadi, Mohammad Reza

    2017-01-01

    Helicobacter pylori (H. pylori) gastric infection is a main cause of inflammatory changes and gastric cancers. The aim of this study was finding the effects of curcumin on oxidative stress and histological changes in chronic gastritis associated with H. pylori. In a randomized clinical trial, patients were divided into two groups: a standard triple therapy group and triple therapy with curcumin group. Endoscopic and histological examinations were measured for all patients before and after 8 weeks. Triple therapy with curcumin treatment group significantly decreased malondialdehyde markers, glutathione peroxides and increased total antioxidant capacity of the gastric mucosa at the end of study compared to baseline and triple regimen groups. In addition, the oxidative damage to DNA was significantly decreased in triple therapy with curcumin group at the end of study compared to baseline and compared to triple therapy (Pgastritis associated by H. pylori.

  13. Role of adjuvant therapy in the treatment of helicobacter pylori infection in children

    Directory of Open Access Journals (Sweden)

    Gerasymenko O.N.

    2014-06-01

    Full Text Available The aim was to study the effect of combined probiotic containing Lactobacillus acidophilus, Bifidobacterium infantis, Enterococcus faecium, on H.pylori eradication efficacy in the treatment of children with chronic H.pylori- associated gastroduodenitis in the scheme of "triple" therapy of H.pylori eradication. Determination of total serum Ig M , A, G protein to Ag SagA H. pylori, breathing "Helik" test, rapid urease "Helpil" test ; that of concentration of serum sCD14 was conducted. The study group included 20 children who received standard "triple" eradication therapy for 7 days and 1 caps. of probiotic 3 times a day for 4 weeks, control group (20 children – who received only standard eradication therapy. It is shown that combined use of probiotics in the treatment of Helicobacter pylori infection enhances effectiveness of eradication of H.pylori. In the basis of action of probiotic strains of the drug is an anti-inflammatory effect mediated by the impact on non-specific mechanisms of innate immunity, provided by molecular mechanism responsible for induction of sCD14 synthesis.

  14. [Topical immunomodulation in the treatment of herpetic infections in HIV-infected patients].

    Science.gov (United States)

    Shul'diakov, A A; Barkhatova, T S; Zubareva, E V; Satarova, S A; Perminova, T A

    2012-01-01

    The efficiency of cycloferon liniment in combined treatment of herpetic infection in patients with latent form of HIV infection has been assess by observations of 40 patients divided into two groups. In the first group, the standard treatment was supplemented with the application of cycloferon liniment twice a day during 7 days; in the second group, the therapy was conducted according to standard recommendations. It was established that the application of cycloferon liniment in combination with standard therapy in patients with relapse of herpetic infection against the background of HIV infection ensures faster disappearance of general infectious syndrome, decreases the period of eruptions and the duration of local inflammations, and accelerates the epithelialization of erosions.

  15. Outcome after VAC® therapy for infected bypass grafts in the lower limb.

    Science.gov (United States)

    Acosta, S; Monsen, C

    2012-09-01

    To assess the outcome of vacuum-assisted wound closure (VAC(®)) therapy for infected bypass grafts. A retrospective 7-year review of patient records from 2004 to 2011 of all patients receiving VAC(®) therapy for infected bypass grafts. Thirty-seven patients with 42 wounds and 45 infected bypass (28 synthetic) grafts received VAC(®) treatment. Two serious bleeding episodes from the suture lines occurred. The median VAC(®) therapy time was 20 days. The proportion of patent bypass grafts was 91% (41/45) at a median time of 3.5 months from the start of VAC(®) therapy. Five patients with seven bypasses had persistent infection or re-infection, and the total graft preservation rate was 76% (34/45). The median follow-up time was 15 months. The presence of two infected bypass grafts in one groin wound was associated with an increased major amputation rate (hazard ratio (HR) 7.4 [95% confidence interval (CI) 2.0-27.5]), and synthetic graft infection (HR 5.0 [95% CI 1.5-17.4]) and non-healed wound (HR 3.6 [95% CI 1.5-8.7]) were associated with mortality. VAC(®) therapy of infected bypass grafts was able to induce effective wound healing without compromising the early bypass function. Two infected synthetic bypasses in the wound were associated with the highest risk of adverse outcome. Copyright © 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  16. Interleukin-2 therapy in patients with HIV infection

    DEFF Research Database (Denmark)

    Abrams, D; Lévy, Y; Losso, M H

    2009-01-01

    Interleukin-2 in HIV-Infected Patients with Low CD4+ Counts under Active Antiretroviral Therapy (SILCAAT) study and the Evaluation of Subcutaneous Proleukin in a Randomized International Trial (ESPRIT). In each, patients infected with the human immunodeficiency virus (HIV) who had CD4+ cell counts of either...

  17. Artificial intelligence in drug combination therapy.

    Science.gov (United States)

    Tsigelny, Igor F

    2018-02-09

    Currently, the development of medicines for complex diseases requires the development of combination drug therapies. It is necessary because in many cases, one drug cannot target all necessary points of intervention. For example, in cancer therapy, a physician often meets a patient having a genomic profile including more than five molecular aberrations. Drug combination therapy has been an area of interest for a while, for example the classical work of Loewe devoted to the synergism of drugs was published in 1928-and it is still used in calculations for optimal drug combinations. More recently, over the past several years, there has been an explosion in the available information related to the properties of drugs and the biomedical parameters of patients. For the drugs, hundreds of 2D and 3D molecular descriptors for medicines are now available, while for patients, large data sets related to genetic/proteomic and metabolomics profiles of the patients are now available, as well as the more traditional data relating to the histology, history of treatments, pretreatment state of the organism, etc. Moreover, during disease progression, the genetic profile can change. Thus, the ability to optimize drug combinations for each patient is rapidly moving beyond the comprehension and capabilities of an individual physician. This is the reason, that biomedical informatics methods have been developed and one of the more promising directions in this field is the application of artificial intelligence (AI). In this review, we discuss several AI methods that have been successfully implemented in several instances of combination drug therapy from HIV, hypertension, infectious diseases to cancer. The data clearly show that the combination of rule-based expert systems with machine learning algorithms may be promising direction in this field. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Early treatment failure in concurrent dengue and mixed malaria species infection with suspected resistance to artemisinin combination therapy from a tertiary care center in Delhi: a case report.

    Science.gov (United States)

    Saksena, Rushika; Matlani, Monika; Singh, Vineeta; Kumar, Amit; Anveshi, Anupam; Kumar, Dilip; Gaind, Rajni

    2017-01-01

    Concurrent dengue and mixed malaria infections in a single patient present with overlapping clinical manifestations which pose a diagnostic challenge and management dilemma in areas of common endemicities. We report a case of a young male who tested positive for both Plasmodium vivax and Plasmodium falciparum along with dengue infection. He showed signs of early treatment failure to artemisinin combination therapy (artesunate with sulfadoxine+pyrimethamine). Molecular analysis for the drug resistance genes viz: chloroquine resistance ( pfcrt ), multidrug resistance ( pfmdr-1 ), sulfadoxine ( pfdhps ), pyrimethamine ( pfdhfr ), and artemisinin resistance ( keltch 13 ) was performed. A rise in parasitemia from treatment. Mutations in pfcrt , pfmdr-1 , pfdhfr , and pfdhps genes were detected as a possible cause of treatment failure. Increased severity, overlapping symptoms, and suspected resistance to treatment warrants a multidimensional diagnostic approach and diligent therapeutic monitoring.

  19. Safe interruption of maintenance therapy against previous infection with four common HIV-associated opportunistic pathogens during potent antiretroviral therapy

    DEFF Research Database (Denmark)

    Kirk, Ole; Reiss, Peter; Uberti-Foppa, Caterina

    2002-01-01

    maintenance therapy for cytomegalovirus (CMV) end-organ disease, disseminated Mycobacterium avium complex (MAC) infection, cerebral toxoplasmosis, and extrapulmonary cryptococcosis in patients receiving antiretroviral therapy. DESIGN: Observational study. SETTING: Seven European HIV cohorts. PATIENTS: 358...... identified: 162 for CMV disease, 103 for MAC infection, 75 for toxoplasmosis, and 39 for cryptococcosis. During 781 person-years of follow-up, five patients had relapse. Two relapses (one of CMV disease and one of MAC infection) were diagnosed after maintenance therapy was interrupted when the CD4 lymphocyte....... One relapse (toxoplasmosis) was diagnosed after maintenance therapy interruption at a CD4 lymphocyte count greater than 200 x 10(6) cells/L for 15 months. The overall incidences of recurrent CMV disease, MAC infection, toxoplasmosis, and cryptococcosis were 0.54 per 100 person-years (95% CI, 0.07 to 1...

  20. Antimicrobial therapy for the treatment of opportunistic infections in HIV/AIDS patients: a critical appraisal

    Directory of Open Access Journals (Sweden)

    Seddon J

    2011-04-01

    Full Text Available Jo Seddon1, Sanjay Bhagani21Department of Infectious Diseases, Imperial College Healthcare NHS Trust, London, UK; 2Department of Infection and Immunity, Royal Free Hospital NHS Trust, London, UKAbstract: The widespread use of antiretroviral therapy (ART has entirely changed the management of human immunodeficiency virus (HIV infection and dramatically reduced the rates of opportunistic infections (OI. However, OI continue to cause significant morbidity and mortality in both developed countries, where presentation with advanced HIV infection is common, and also in developing countries where ART is less widely available. Evidence to direct OI guidelines is partly limited by the fact that many large-scale studies date from the pre-ART era and more recent studies are sometimes poorly powered due to the falling rates of OI. Treatment of OI is now known to be as much about antimicrobials as about immune reconstitution with ART, and recent studies help guide the timing of initiation of ART in different infections. OI have also become complicated by the immune reconstitution inflammatory syndrome phenomenon which may occur once successful immune recovery begins. Trimethoprim-sulfamethoxazole has long been one of the most important antibiotics in the treatment and prevention of OI and remains paramount. It has a broad spectrum of activity against Pneumocystis jiroveci, toxoplasmosis, and bacterial infections and has an important role to play in preventing life-threatening OI. New advances in treating OI are coming from a variety of quarters: in cytomegalovirus eye disease, the use of oral rather than intravenous drugs is changing the face of therapy; in cryptococcal meningitis, improved drug formulations and combination therapy is improving clearance rates and reducing drug toxicities; and in gut disease, the possibility of rapid immune restitution with ART is replacing the need for antimicrobials against cryptosporidia and microsporidia.Keywords: HIV

  1. Electronic medication monitoring-informed counseling to improve adherence to combination anti-retroviral therapy and virologic treatment outcomes: a meta-analysis

    NARCIS (Netherlands)

    Langebeek, Nienke; Nieuwkerk, Pythia

    2015-01-01

    Adherence to combination anti-retroviral therapy for HIV infection is a primary determinant of treatment success, but is often suboptimal. Previous studies have suggested that electronic medication monitoring-informed counseling is among the most effective adherence intervention components. Our

  2. Immune control of HIV-1 infection after therapy interruption: immediate versus deferred antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Bernaschi Massimo

    2009-10-01

    Full Text Available Abstract Background The optimal stage for initiating antiretroviral therapies in HIV-1 bearing patients is still a matter of debate. Methods We present computer simulations of HIV-1 infection aimed at identifying the pro et contra of immediate as compared to deferred Highly Active Antiretroviral Therapy (HAART. Results Our simulations highlight that a prompt specific CD8+ cytotoxic T lymphocytes response is detected when therapy is delayed. Compared to very early initiation of HAART, in deferred treated patients CD8+ T cells manage to mediate the decline of viremia in a shorter time and, at interruption of therapy, the virus experiences a stronger immune pressure. We also observe, however, that the immunological effects of the therapy fade with time in both therapeutic regimens. Thus, within one year from discontinuation, viral burden recovers to the value at which it would level off in the absence of therapy. In summary, simulations show that immediate therapy does not prolong the disease-free period and does not confer a survival benefit when compared to treatment started during the chronic infection phase. Conclusion Our conclusion is that, since there is no therapy to date that guarantees life-long protection, deferral of therapy should be preferred in order to minimize the risk of adverse effects, the occurrence of drug resistances and the costs of treatment.

  3. Advances in combination therapy of lung cancer

    DEFF Research Database (Denmark)

    Wu, Lan; Leng, Donglei; Cun, Dongmei

    2017-01-01

    Lung cancer is a complex disease caused by a multitude of genetic and environmental factors. The progression of lung cancer involves dynamic changes in the genome and a complex network of interactions between cancer cells with multiple, distinct cell types that form tumors. Combination therapy......, including small molecule drugs and biopharmaceuticals, which make the optimization of dosing and administration schedule challenging. This article reviews the recent advances in the design and development of combinations of pharmaceuticals for the treatment of lung cancer. Focus is primarily on rationales...... for the selection of specific combination therapies for lung cancer treatment, and state of the art of delivery technologies and dosage regimens for the combinations, tested in preclinical and clinical trials....

  4. Study of the use of probiotic foods as a complement of the conventional antibiotic-therapy for the treatment of Helicobacter pylori infection in children and it's use as a prophylactic therapy in the reinfection by this pathogen

    International Nuclear Information System (INIS)

    Zubillaga, M.; Goldman, C.; Caro, R.; Boccio, J.; Weill, R.; Postaire, E.

    2000-01-01

    Helicobacter pylori infection is very frequent in children in developing countries. Studies on eradication regimens and its complications are not well documented. The European Helicobacter pylori Study Group strongly recommends that treatment should be with proton pump inhibitor based triple therapy, consisting of a proton pump inhibitor and two of the following: clarithromycin, a nitroimidazole (metronidazole or tinidazole) and amoxycillin in various combinations. Recent advances in probiotic research show much promise in a new product development of functional foods based on milk. Among the reported beneficial effects of consuming certain strains of cultures or their metabolites, or both are control of ulcers related to Helicobacter pylori. Kefir seems to be a potential probiotic to control Helicobacter pylori infection. In this study 2 groups of 10 children each which demonstrate to be Helicobacter pylori positive will be treated as follows: Group 1: antibiotic treatment + placebo (fluid milk) and Group 2: antibiotic treatment + kefir. The Triple Therapy consists in the combination of two antibiotics (amoxycillin and clarithromycin) with a proton pump inhibitor (Lansoprazole). In all the cases, the post-treatment control will be performed by the 13 C UBT 2 months after the end of the treatment. Once the infection is eradicated, the group who received the antibiotic-therapy with milk (placebo) as well as the group who received the antibiotic-therapy with the probiotic under study will continue with the administration of the milk and/or probiotic food during one year. During this period, the children will be submitted to post-treatment controls performed by the 13 C UBT every three months. We expect to find that the group that received the triple therapy in combination with the probiotic food (kefir) would have less recidiva rates for the Helicobacter pylori infection than the group that received the triple therapy with the placebo (fluid milk). (author)

  5. Study of the use of probiotic foods as a complement of the conventional antibiotic-therapy for the treatment of Helicobacter pylori infection in children and it's use as a prophylactic therapy in the reinfection by this pathogen

    Energy Technology Data Exchange (ETDEWEB)

    Zubillaga, M; Goldman, C; Caro, R; Boccio, J [Laboratorio de Radioisotopos, Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires, Buenos Aires (Argentina); Weill, R [Departamento de Industrias Agrarias, Facultad de Agronomia, Universidad de Moron, Buenos Aires (Argentina); Postaire, E [Research International Center Daniel Carasso (France)

    2000-07-01

    Helicobacter pylori infection is very frequent in children in developing countries. Studies on eradication regimens and its complications are not well documented. The European Helicobacter pylori Study Group strongly recommends that treatment should be with proton pump inhibitor based triple therapy, consisting of a proton pump inhibitor and two of the following: clarithromycin, a nitroimidazole (metronidazole or tinidazole) and amoxycillin in various combinations. Recent advances in probiotic research show much promise in a new product development of functional foods based on milk. Among the reported beneficial effects of consuming certain strains of cultures or their metabolites, or both are control of ulcers related to Helicobacter pylori. Kefir seems to be a potential probiotic to control Helicobacter pylori infection. In this study 2 groups of 10 children each which demonstrate to be Helicobacter pylori positive will be treated as follows: Group 1: antibiotic treatment + placebo (fluid milk) and Group 2: antibiotic treatment + kefir. The Triple Therapy consists in the combination of two antibiotics (amoxycillin and clarithromycin) with a proton pump inhibitor (Lansoprazole). In all the cases, the post-treatment control will be performed by the {sup 13}C UBT 2 months after the end of the treatment. Once the infection is eradicated, the group who received the antibiotic-therapy with milk (placebo) as well as the group who received the antibiotic-therapy with the probiotic under study will continue with the administration of the milk and/or probiotic food during one year. During this period, the children will be submitted to post-treatment controls performed by the {sup 13}C UBT every three months. We expect to find that the group that received the triple therapy in combination with the probiotic food (kefir) would have less recidiva rates for the Helicobacter pylori infection than the group that received the triple therapy with the placebo (fluid milk). (author)

  6. Predictors and correlates of adherence to combination antiretroviral therapy (ART) for chronic HIV infection: a meta-analysis

    NARCIS (Netherlands)

    Langebeek, Nienke; Gisolf, Elizabeth H.; Reiss, Peter; Vervoort, Sigrid C.; Hafsteinsdóttir, Thóra B.; Richter, Clemens; Sprangers, Mirjam A. G.; Nieuwkerk, Pythia T.

    2014-01-01

    Adherence to combination antiretroviral therapy (ART) is a key predictor of the success of human immunodeficiency virus (HIV) treatment, and is potentially amenable to intervention. Insight into predictors or correlates of non-adherence to ART may help guide targets for the development of

  7. Transient Serotonin Toxicity Evoked by Combination of Electroconvulsive Therapy and Fluoxetine

    DEFF Research Database (Denmark)

    Klysner, René; Bjerg Bendsen, Birgitte; Hansen, Maja Soon

    2014-01-01

    The serotonin syndrome has been described only in rare instances for electroconvulsive therapy combined with an antidepressant medication. We describe a case of serotonin toxicity induced by electroconvulsive therapy in combination with fluoxetine.......The serotonin syndrome has been described only in rare instances for electroconvulsive therapy combined with an antidepressant medication. We describe a case of serotonin toxicity induced by electroconvulsive therapy in combination with fluoxetine....

  8. Kaposi Sarcoma Risk in HIV-Infected Children and Adolescents on Combination Antiretroviral Therapy From Sub-Saharan Africa, Europe, and Asia.

    Science.gov (United States)

    Rohner, Eliane; Schmidlin, Kurt; Zwahlen, Marcel; Chakraborty, Rana; Clifford, Gary; Obel, Niels; Grabar, Sophie; Verbon, Annelies; Noguera-Julian, Antoni; Collins, Intira Jeannie; Rojo, Pablo; Brockmeyer, Norbert; Campbell, Maria; Chêne, Geneviève; Prozesky, Hans; Eley, Brian; Stefan, D Cristina; Davidson, Alan; Chimbetete, Cleophas; Sawry, Shobna; Davies, Mary-Ann; Kariminia, Azar; Vibol, Ung; Sohn, Annette; Egger, Matthias; Bohlius, Julia

    2016-11-01

    The burden of Kaposi sarcoma (KS) in human immunodeficiency virus (HIV)-infected children and adolescents on combination antiretroviral therapy (cART) has not been compared globally. We analyzed cohort data from the International Epidemiologic Databases to Evaluate AIDS and the Collaboration of Observational HIV Epidemiological Research in Europe. We included HIV-infected children aged origin, sex, cART start year, age, and HIV/AIDS stage at cART initiation. We included 24 991 children from eastern Africa, southern Africa, Europe and Asia; 26 developed KS after starting cART. Incidence rates per 100 000 person-years (PYs) were 86 in eastern Africa (95% confidence interval [CI], 55-133), 11 in southern Africa (95% CI, 4-35), and 81 (95% CI, 26-252) in children of sub-Saharan African (SSA) origin in Europe. The KS incidence rates were 0/100 000 PYs in children of non-SSA origin in Europe (95% CI, 0-50) and in Asia (95% CI, 0-27). KS risk was lower in girls than in boys (adjusted HR [aHR], 0.3; 95% CI, .1-.9) and increased with age (10-15 vs 0-4 years; aHR, 3.4; 95% CI, 1.2-10.1) and advanced HIV/AIDS stage (CDC stage C vs A/B; aHR, 2.4; 95% CI, .8-7.3) at cART initiation. HIV-infected children from SSA but not those from other regions, have a high risk of developing KS after cART initiation. Early cART initiation in these children might reduce KS risk. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  9. [Drug susceptibility test guided therapy and novel empirical quadruple therapy for Helicobacter pylori infection: a network Meta-analysis].

    Science.gov (United States)

    Gou, Q Y; Yu, R B; Shi, R H

    2017-05-10

    Objective: To compare the efficacy and the risk of adverse effect of drug susceptibility test guided therapy and novel empirical quadruple therapy for Helicobacter ( H .) pylori infection. Methods: Literature retrieval was conducted by using major databases. Related papers published up to June 2015 were considered eligible if they were randomized control trials comparing different pharmacological formulations for H. pylori infection and used in a network Meta-analysis and a single rate Meta-analysis to evaluate the relative and absolute rates of H. pylori eradication and the risk of adverse effect. The Jadad score was used to evaluate the methodological quality. Funnel plot was constructed to evaluate the risk of publication bias. Begg's rank correlation test or Egger's regression intercept test was done for the asymmetry of funnel plot. Results: Twenty randomized control trials for the treatment of 6 753 initial treated patients with H. pylori infection were included. Drug susceptibility test guided therapy was significantly superior to concomitant therapy, hybrid therapy, sequential therapy and bismuth quadruple therapy. The culture-based therapy had the highest likelihood of improving clinical efficacy, with lowest risk of adverse effect. Concomitant therapy had the highest probability of causing adverse effect despite its effectiveness. Hybrid therapy and bismuth quadruple therapy were associated with lower risk of adverse effect and higher effectiveness. Conclusion: Drug susceptibility test guided therapy showed superiority to other 4 interventions for H. pylori eradication mentioned above. Hybrid therapy and bismuth quadruple therapy might be applied in the settings where the culture-based strategy is not available.

  10. Asthma Severity in patients initiating controller monotherapy versus combination therapy.

    Science.gov (United States)

    Diette, Gregory B; Fuhlbrigge, Anne L; Allen-Ramey, Felicia; Hopper, April; Sajjan, Shiva G; Markson, Leona E

    2011-04-01

    Asthma treatment guidelines recommend medications based on the level of asthma control. To evaluate differences in asthma control between patients who initiated asthma controller monotherapy versus combination therapy. Children (5-16 years; n = 488) and adults (17-80 years; n = 530) with asthma and no controller therapy in the prior 6 months were included. Telephone surveys were conducted within 5 days of filling a new asthma controller prescription with either the caregiver of children or the adult patient. Demographics, asthma control before therapy, and asthma-related resource use were assessed for patients initiating monotherapy (filling one asthma controller prescription) and combination therapy (filling more than one controller medication or a fixed-dose combination). Mean pediatric age was 10 years; 53% were male. Mean adult age was 47 years; 25% were male. There were no significant differences in asthma control score between patients receiving monotherapy and combination therapy. Children on combination therapy did not have more nighttime awakening or short-acting β-agonist use but were more likely to have been hospitalized due to asthma attack (p = .05) and have more unscheduled (p = .0374) and scheduled (p = .009) physician visits. Adults on combination therapy were more likely to have been hospitalized due to asthma attack (p asthma (p asthma control scores in the 4 weeks before index medication suggests that asthma severity during a treatment-free period did not differ significantly for patients initiating controller monotherapy versus combination therapy. From these findings, it appears that although physicians may not focus on asthma control when choosing the intensity of initial controller therapy, the intensity of health-care encounters may be an influence.

  11. Analysis of combination drug therapy to develop regimens with shortened duration of treatment for tuberculosis.

    Directory of Open Access Journals (Sweden)

    George L Drusano

    Full Text Available Tuberculosis remains a worldwide problem, particularly with the advent of multi-drug resistance. Shortening therapy duration for Mycobacterium tuberculosis is a major goal, requiring generation of optimal kill rate and resistance-suppression. Combination therapy is required to attain the goal of shorter therapy.Our objective was to identify a method for identifying optimal combination chemotherapy. We developed a mathematical model for attaining this end. This is accomplished by identifying drug effect interaction (synergy, additivity, antagonism for susceptible organisms and subpopulations resistant to each drug in the combination.We studied the combination of linezolid plus rifampin in our hollow fiber infection model. We generated a fully parametric drug effect interaction mathematical model. The results were subjected to Monte Carlo simulation to extend the findings to a population of patients by accounting for between-patient variability in drug pharmacokinetics.All monotherapy allowed emergence of resistance over the first two weeks of the experiment. In combination, the interaction was additive for each population (susceptible and resistant. For a 600 mg/600 mg daily regimen of linezolid plus rifampin, we demonstrated that >50% of simulated subjects had eradicated the susceptible population by day 27 with the remaining organisms resistant to one or the other drug. Only 4% of patients had complete organism eradication by experiment end.These data strongly suggest that in order to achieve the goal of shortening therapy, the original regimen may need to be changed at one month to a regimen of two completely new agents with resistance mechanisms independent of the initial regimen. This hypothesis which arose from the analysis is immediately testable in a clinical trial.

  12. Effectiveness of medication / auricular therapy / phyto-therapy combination in the treatment of hypertensive patients

    Directory of Open Access Journals (Sweden)

    José Ramón Martínez Pérez

    2015-10-01

    Full Text Available Background: hypertension is one of the main cardiovascular risk factors, so its control improves the life expectancy of patients.Objective: to assess the effects of a treatment combining medication with auricular therapy and phyto-therapy in hypertensive patients assisted at the health area of ”Romárico Oro” Polyclinic, in Puerto Padre, Las Tunas province.Methods: an intervention study was carried out in 68 hypertensive patients of the health area of “Romárico Oro” Polyclinic in Puerto Padre from April, 2013 to April, 2014. The patients were distributed at random into two equal groups; the first received medication combined with auricular therapy and phyto-therapy, while the second one received only medication. The statistical analysis was done by means of Statistic system, t-student and Chi-Square tests were used and p< or =0.05 was considered as level of statistical significance.Results: by the end of the intervention, 73, 53% of the patients of the group with the combination of drug treatment and auricular therapy and phyto-therapy were controlled. In this group, the diastolic filling pressure diminished to 2, 2 mm Hg and the systolic gradient to 3, 66 mm, regarding the group treated only with drugs. Only one patient, representing the 2, 94% showed adverse reaction to the natural and traditional treatment.Conclusions: the combination of medication with auricular therapy and phyto-therapy proved to be effective, corroborated by a significant decrease of quantity of crisis, diastolic and systolic filling pressure values and increase of number of patients with their disease controlled; the report of only one complication shows the innocuousness of the auricular therapy and phyto-therapy treatment.

  13. Combination immunotherapy in the treatment of chronic bilateral panuveitis and uveitic glaucoma during acute dengue fever infection in the Caribbean.

    Science.gov (United States)

    Stewart, Kevin P; Tawakol, Jan B; Khan, Tasnim; Capriotti, Joseph A

    2015-01-01

    Ocular manifestations of the dengue fever virus include bilateral panuveitis that can occur after the acute systemic infection has resolved. In most reported cases, the inflammation resolves with topical or systemic steroid therapy. We report a case of chronic, refractory bilateral panuveitis and uveitic glaucoma that began during the acute phase of the systemic infection and required treatment with oral steroids, multiple steroid-sparing agents, and surgical therapy for glaucoma. A 22-year-old male with acute systemic dengue fever presented with bilateral pain and decreased vision. Clinical examination revealed bilateral panuveitis with elevated intraocular pressures. Management required oral steroids, mycophenolate mofetil, cyclosporine, and bilateral glaucoma valve implantation. This case highlights the fact that dengue-associated panuveitis can begin in the acute stage of systemic infection and persist long after convalescence with progression to chronic bilateral panuveitis and uveitic glaucoma. Dengue-associated chronic panuveitis with uveitic glaucoma may be effectively managed with a combination of steroid-sparing oral immunosuppression and glaucoma surgery. This is, to our knowledge, the first case of bilateral refractory dengue-associated panuveitis from the Caribbean treated with combination steroid-sparing oral immunosuppression and bilateral glaucoma valve implantation.

  14. Vacuum assisted closure therapy in the treatment of mesh infection after hernia repair.

    Science.gov (United States)

    Tamhankar, A P; Ravi, K; Everitt, N J

    2009-10-01

    Mesh related infection after prosthetic abdominal wall hernia repair is a difficult clinical problem, particularly in an era of evolving microbial resistance. Commonly advocated treatment for such infection involves complete mesh excision which usually leaves a complicated weak wound. We report the use ofVAC therapy for mesh infections that allows mesh preservation leaving a sound wound. From june 2002 to January 2007, four patients with mesh related infection after abdominal wall hernia repair were treated with VAC therapy. Patients' notes were reviewed to gather clinical details. Mesh infection was evident after a variable period (day three to eight years) following hernia repair. Of the four patients, one had infection with methicillin resistant Staphylococcus aureus (MRSA), while the bacteriological cultures from two confirmed Staphylococcus aureus in one and a mixture of Pseudomonas and enterococcus species in the other. One patient failed to show significant bacterial growth on pus swab culture, having had prior broad-spectrum antibiotic treatment for mesh infection. Three patients had complete mesh preservation and one had partial mesh excision. All patients were treated with VAC therapy, following the drainage of their operation sites, until the visible mesh was covered with granulation (one to seven weeks). No patient had a recurrent hernia after complete wound healing. VAC therapy allows salvage of infected exposed mesh by promoting granulation through the mesh. Judicious use of VAC therapy may prevent the need of mesh excision and its wound related complications.

  15. Onset of Type 1 Diabetes Mellitus During Pegylated-interferon Alfa and Ribavirin Therapy for Chronic Hepatitis C Virus Infection

    Science.gov (United States)

    Ranganathan, Raghini; Janarthanan, Krishnaveni; Rajasekaran, Senthilkumar

    2012-01-01

    A 16-year-old female was treated with pegylated-interferon (PEG-IFN) alfa (a)-2b and ribavirin combination therapy for chronic hepatitis C virus (HCV) infection. She attained rapid virological response. She presented with diabetic ketoacidosis after 41 weeks of therapy. Anti-glutamic acid decarboxylase antibodies and islet cell antibodies were negative. Her fasting serum C-peptide level was <0.1 ng/mL, and the treatment course was completed. This case underlines the importance of periodic plasma glucose monitoring in patients during and after PEG-IFN and ribavirin therapy. PMID:25755410

  16. The promise of bacteriophage therapy for Burkholderia cepacia complex respiratory infections.

    Directory of Open Access Journals (Sweden)

    Diana Dawn Semler

    2012-01-01

    Full Text Available In recent times, increased attention has been given to evaluating the efficacy of phage therapy, especially in scenarios where the bacterial infectious agent of interest is highly antibiotic resistant. In this regard, phage therapy is especially applicable to infections caused by the Burkholderia cepacia complex (BCC since members of the BCC are antibiotic pan-resistant. Current studies in BCC phage therapy are unique from many other avenues of phage therapy research in that the research is not only comprised of phage isolation, in vitro phage characterization and in vivo infection model efficacy, but also adapting aerosol drug delivery techniques to aerosol phage formulation delivery and storage.

  17. Long-term effectiveness of highly active antiretroviral therapy (HAART) in perinatally HIV-infected children in Denmark

    DEFF Research Database (Denmark)

    Bracher, Linda; Valerius, Niels Henrik; Rosenfeldt, Vibeke

    2007-01-01

    children treated with HAART. Initial HAART included 2 nucleoside reverse-transcriptase inhibitors in combination with either a protease inhibitor (n =38) or a non-nucleoside reverse-transcriptase inhibitor (n =12). 19 (39%) patients were previously treated with mono- or dual therapy. Baseline......The long-term impact of highly active antiretroviral therapy (HAART) on HIV-1 infected children is not well known. The Danish Paediatric HIV Cohort Study includes all patients ... characteristics were median CD4 percentage 14% and HIV-RNA viral load 4.9 log(10). Within the first 12 weeks of therapy approximately 60% achieved HIV-RNA viral load children changed the components of HAART. The proportion of children with CD4...

  18. Management of hepatitis C infection in the era of direct-acting antiviral therapy

    Science.gov (United States)

    Zain, L. H.; Sungkar, T.

    2018-03-01

    Hepatitis C viral infection globally affects millions of people and commonly results in debilitating complications and mortality. Initial mainstay therapy consisted of pegylated interferon α (pegIFNα) with additional ribavirin that showed unsatisfactory cure rate, common side effects and complicated dosing, contributing to high discontinuation rate. Over the last few years, newer antivirals have been extensively studied, that are Direct-Acting Antivirals (DAAs). Specifically targeting viral protein mainly during replication phase, DAAs showed greater cure rate (commonly measured as sustained virologic response), improved safety profile and shorter treatment duration compared to traditional interferon-ribavirin therapy. Current guidelines have also included Interferon-free, often ribavirin-free, DAAs combinations that suggest promising outcomes. The current review highlights development of rapidly growing hepatitis C treatment including DAAs recommendations.

  19. In Vitro Assessment of Combined Polymyxin B and Minocycline Therapy against Klebsiella pneumoniae Carbapenemase (KPC)-Producing K. pneumoniae.

    Science.gov (United States)

    Huang, Dennis; Yu, Brenda; Diep, John K; Sharma, Rajnikant; Dudley, Michael; Monteiro, Jussimara; Kaye, Keith S; Pogue, Jason M; Abboud, Cely Saad; Rao, Gauri G

    2017-07-01

    The multidrug resistance profiles of Klebsiella pneumoniae carbapenemase (KPC) producers have led to increased clinical polymyxin use. Combination therapy with polymyxins may improve treatment outcomes, but it is uncertain which combinations are most effective. Clinical successes with intravenous minocycline-based combination treatments have been reported for infections caused by carbapenemase-producing bacteria. The objective of this study was to evaluate the in vitro activity of polymyxin B and minocycline combination therapy against six KPC-2-producing K. pneumoniae isolates (minocycline MIC range, 2 to 32 mg/liter). Polymyxin B monotherapy (0.5, 1, 2, 4, and 16 mg/liter) resulted in a rapid reduction of up to 6 log in bactericidal activity followed by regrowth by 24 h. Minocycline monotherapy (1, 2, 4, 8, and 16 mg/liter) showed no reduction of activity of >1.34 log against all isolates, although concentrations of 8 and 16 mg/liter prolonged the time to regrowth. When the therapies were used in combination, rapid bactericidal activity was followed by slower regrowth, with synergy (60 of 120 combinations at 24 h, 19 of 120 combinations at 48 h) and additivity (43 of 120 combinations at 24 h, 44 of 120 combinations at 48 h) against all isolates. The extent of killing was greatest against the more susceptible polymyxin B isolates (MICs of ≤0.5 mg/liter) regardless of the minocycline MIC. The pharmacodynamic activity of combined polymyxin B-minocycline therapy against KPC-producing K. pneumoniae is dependent on polymyxin B susceptibility. Further in vitro and animal studies must be performed to fully evaluate the efficacy of this drug combination. Copyright © 2017 American Society for Microbiology.

  20. Nanomedicine of synergistic drug combinations for cancer therapy - Strategies and perspectives.

    Science.gov (United States)

    Zhang, Rui Xue; Wong, Ho Lun; Xue, Hui Yi; Eoh, June Young; Wu, Xiao Yu

    2016-10-28

    Nanomedicine of synergistic drug combinations has shown increasing significance in cancer therapy due to its promise in providing superior therapeutic benefits to the current drug combination therapy used in clinical practice. In this article, we will examine the rationale, principles, and advantages of applying nanocarriers to improve anticancer drug combination therapy, review the use of nanocarriers for delivery of a variety of combinations of different classes of anticancer agents including small molecule drugs and biologics, and discuss the challenges and future perspectives of the nanocarrier-based combination therapy. The goal of this review is to provide better understanding of this increasingly important new paradigm of cancer treatment and key considerations for rational design of nanomedicine of synergistic drug combinations for cancer therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Effectiveness of Dry Cow Therapy Comprising Antibiotic Treatment, Internal Teat Sealant, and α-Tocopherol Against New Intramammary Infections in Cows

    Directory of Open Access Journals (Sweden)

    Cengiz Mehmet

    2015-04-01

    Full Text Available The aim of this study was to evaluate the preventive effectiveness of dry cow therapy based on antibiotic, internal teat sealant, and α-tocopherol administered separately or in various combinations at drying-off The study was performed on 322 uninfected quarters of 95 cows originating from three dairy herds. The new intramammary infection rates after calving were measured to evaluate the effectiveness. The quarters were divided into six groups differing in treatment, namely: control group (group C, n = 40 and five treatment groups. Treatment groups were arranged as follows: group A (antibiotic alone, n = 81, group AS (antibiotic + sealant, n = 40, group AST (antibiotic + sealant + α-tocopherol, n = 40, group T (α-tocopherol alone, n = 40, group S (sealant alone, n = 81. New infection rate amounted to 47.5% in group C. The treatment in group AST significantly prevented from the occurrence of new intramammary infections (12.5%, P 0.05, although the use of the sealant alone (group S decreased the risk of new infection (24.7%, P 0.05. Increased α-tocopherol level (P < 0.05 was detected after calving in the quarters from cows that received α-tocopherol injections. In conclusion, the combination of antibiotic, internal teat sealant, and α-tocopherol used in dry cow therapy showed a significantly better preventive effect against new intramammary infections, than the therapeutics administered separately.

  2. Reference curves for CD4 T-cell count response to combination antiretroviral therapy in HIV-1-infected treatment-naïve patients

    DEFF Research Database (Denmark)

    Bouteloup, V; Sabin, C; Mocroft, A

    2017-01-01

    OBJECTIVES: The aim of this work was to provide a reference for the CD4 T-cell count response in the early months after the initiation of combination antiretroviral therapy (cART) in HIV-1-infected patients. METHODS: All patients in the Collaboration of Observational HIV Epidemiological Research....... Unadjusted and adjusted references curves and predictions were obtained using quantile regressions. RESULTS: A total of 28 992 patients were included in the study. The median CD4 T-cell count at treatment initiation was 249 [interquartile range (IQR) 150, 336] cells/μL. The median observed CD4 counts at 6, 9...... and 12 months were 382 (IQR 256, 515), 402 (IQR 274, 543) and 420 (IQR 293, 565) cells/μL. The two main factors explaining the variation of CD4 count at 6 months were AIDS stage and CD4 count at cART initiation. A CD4 count increase of ≥ 100 cells/mL is generally required in order that patients stay 'on...

  3. Intravenous/oral ciprofloxacin therapy versus intravenous ceftazidime therapy for selected bacterial infections.

    Science.gov (United States)

    Gaut, P L; Carron, W C; Ching, W T; Meyer, R D

    1989-11-30

    The efficacy and toxicity of sequential intravenous and oral ciprofloxacin therapy was compared with intravenously administered ceftazidime in a prospective, randomized, controlled, non-blinded trial. Thirty-two patients (16 patients receiving ciprofloxacin and 16 patients receiving ceftazidime) with 38 infections caused by susceptible Pseudomonas aeruginosa, enteric gram-negative rods, Salmonella group B, Serratia marcescens, Pseudomonas cepacia, and Xanthomonas maltophilia at various sites were evaluable for determination of efficacy. Length of therapy varied from seven to 25 days. Concomitant antimicrobials included intravenously administered beta-lactams for gram-positive organisms, intravenous/oral metronidazole and clindamycin for anaerobes, and intravenous/local amphotericin B for Candida albicans. Intravenous administration of 200 mg ciprofloxacin every 12 hours to 11 patients produced peak serum levels between 1.15 and 3.12 micrograms/ml; trough levels ranged between 0.08 and 0.86 micrograms/ml. Overall response rates were similar for patients receiving ciprofloxacin and ceftazidime. Emergence of resistance was similar in both groups--one Enterobacter cloacae and two P. aeruginosa became resistant after ciprofloxacin therapy and two P. aeruginosa became resistant after ceftazidime therapy. The frequency of superinfection with a variety of organisms was also similar in both groups. Adverse events related to ciprofloxacin included transient pruritus at the infusion site and generalized rash leading to drug discontinuation (one patient each), and with ceftazidime adverse effects included pain at the site of infusion and the development of allergic interstitial nephritis (one patient each). Overall, intravenous/oral ciprofloxin therapy appears to be as safe and effective as intravenous ceftazidime therapy in the treatment of a variety of infections due to susceptible aerobic gram-negative organisms.

  4. Otitis media in Brazilian human immunodeficiency virus infected children undergoing antiretroviral therapy.

    Science.gov (United States)

    Miziara, I D; Weber, R; Araújo Filho, B Cunha; Pinheiro Neto, C Diógenes

    2007-11-01

    To assess changes in the prevalence of otitis media, associated with the use of highly active antiretroviral therapy, in Brazilian human immunodeficiency virus (HIV) infected children. Division of otorhinolaryngology, Hospital das Clínicas, Sao Paulo University Medical School, Brazil. A cohort of 459 HIV-infected children aged below 13 years. The prevalence of otitis media and the serum cluster of differentiation four glycoprotein T lymphocyte count were compared for children receiving highly active antiretroviral therapy (with protease inhibitors) and those receiving standard antiretroviral therapy (without protease inhibitors). Otitis media was present in 33.1 per cent of the children. Children aged from zero years to five years 11 months receiving highly active antiretroviral therapy had a higher prevalence of acute otitis media (p=0.02) and a lower prevalence of chronic otitis media (p=0.02). Children who were receiving highly active antiretroviral therapy had a mean serum cluster of differentiation four glycoprotein T lymphocyte count greater than that of those who were receiving standard antiretroviral therapy (pBrazilian HIV-infected children was associated with a lower prevalence of chronic otitis media.

  5. Absence of HIV-1 evolution in the gut-associated lymphoid tissue from patients on combination antiviral therapy initiated during primary infection.

    Directory of Open Access Journals (Sweden)

    Teresa H Evering

    2012-02-01

    Full Text Available Mucosal mononuclear (MMC CCR5+CD4+ T cells of the gastrointestinal (GI tract are selectively infected and depleted during acute HIV-1 infection. Despite early initiation of combination antiretroviral therapy (cART, gut-associated lymphoid tissue (GALT CD4+ T cell depletion and activation persist in the majority of HIV-1 positive individuals studied. This may result from ongoing HIV-1 replication and T-cell activation despite effective cART. We hypothesized that ongoing viral replication in the GI tract during cART would result in measurable viral evolution, with divergent populations emerging over time. Subjects treated during early HIV-1 infection underwent phlebotomy and flexible sigmoidoscopy with biopsies prior to and 15-24 months post initiation of cART. At the 2(nd biopsy, three GALT phenotypes were noted, characterized by high, intermediate and low levels of immune activation. A representative case from each phenotype was analyzed. Each subject had plasma HIV-1 RNA levels <50 copies/ml at 2(nd GI biopsy and CD4+ T cell reconstitution in the peripheral blood. Single genome amplification of full-length HIV-1 envelope was performed for each subject pre- and post-initiation of cART in GALT and PBMC. A total of 280 confirmed single genome sequences (SGS were analyzed for experimental cases. For each subject, maximum likelihood phylogenetic trees derived from molecular sequence data showed no evidence of evolved forms in the GALT over the study period. During treatment, HIV-1 envelope diversity in GALT-derived SGS did not increase and post-treatment GALT-derived SGS showed no substantial genetic divergence from pre-treatment sequences within transmitted groups. Similar results were obtained from PBMC-derived SGS. Our results reveal that initiation of cART during acute/early HIV-1 infection can result in the interruption of measurable viral evolution in the GALT, suggesting the absence of de-novo rounds of HIV-1 replication in this compartment

  6. Absence of HIV-1 evolution in the gut-associated lymphoid tissue from patients on combination antiviral therapy initiated during primary infection.

    Science.gov (United States)

    Evering, Teresa H; Mehandru, Saurabh; Racz, Paul; Tenner-Racz, Klara; Poles, Michael A; Figueroa, Amir; Mohri, Hiroshi; Markowitz, Martin

    2012-02-01

    Mucosal mononuclear (MMC) CCR5+CD4+ T cells of the gastrointestinal (GI) tract are selectively infected and depleted during acute HIV-1 infection. Despite early initiation of combination antiretroviral therapy (cART), gut-associated lymphoid tissue (GALT) CD4+ T cell depletion and activation persist in the majority of HIV-1 positive individuals studied. This may result from ongoing HIV-1 replication and T-cell activation despite effective cART. We hypothesized that ongoing viral replication in the GI tract during cART would result in measurable viral evolution, with divergent populations emerging over time. Subjects treated during early HIV-1 infection underwent phlebotomy and flexible sigmoidoscopy with biopsies prior to and 15-24 months post initiation of cART. At the 2(nd) biopsy, three GALT phenotypes were noted, characterized by high, intermediate and low levels of immune activation. A representative case from each phenotype was analyzed. Each subject had plasma HIV-1 RNA levels <50 copies/ml at 2(nd) GI biopsy and CD4+ T cell reconstitution in the peripheral blood. Single genome amplification of full-length HIV-1 envelope was performed for each subject pre- and post-initiation of cART in GALT and PBMC. A total of 280 confirmed single genome sequences (SGS) were analyzed for experimental cases. For each subject, maximum likelihood phylogenetic trees derived from molecular sequence data showed no evidence of evolved forms in the GALT over the study period. During treatment, HIV-1 envelope diversity in GALT-derived SGS did not increase and post-treatment GALT-derived SGS showed no substantial genetic divergence from pre-treatment sequences within transmitted groups. Similar results were obtained from PBMC-derived SGS. Our results reveal that initiation of cART during acute/early HIV-1 infection can result in the interruption of measurable viral evolution in the GALT, suggesting the absence of de-novo rounds of HIV-1 replication in this compartment during

  7. Bacteriophage therapy to combat bacterial infections in poultry.

    Science.gov (United States)

    Wernicki, Andrzej; Nowaczek, Anna; Urban-Chmiel, Renata

    2017-09-16

    Infections in poultry are an economic and health problem in Europe and worldwide. The most common infections are associated with salmonellosis, colibacillosis, campylobacteriosis, and others. The prevalence of Campylobacter-positive poultry flocks in European countries varies from 18% to 90%. In the United States, the prevalence of infected flocks is nearly 90%. A similar percentage of infection has been noted for salmonellosis (about 75-90%) and E. coli (90-95%). The occurence of Clostridium perfringens is a major problem for the poultry industry, with some estimates suggesting colonization of as many as 95% of chickens, resulting in clinical or subclinical infections. In the US, annual economic losses due to Salmonella infections run from $1.188 billion to over $11.588 billion, based on an estimated 1.92 million cases. Similar costs are observed in the case of other types of infections. In 2005 economic losses in the the poultry industry due to mortalities reached 1,000,000 USD.Infections caused by these pathogens, often through poultry products, are also a serious public health issue.The progressive increase in the number of multi-drug resistant bacteria and the complete ban on the use of antibiotics in livestock feed in the EU, as well as the partial ban in the US, have led to the growth of research on the use of bacteriophages to combat bacterial infections in humans and animals.The high success rate and safety of phage therapy in comparison with antibiotics are partly due to their specificity for selected bacteria and the ability to infect only one species, serotype or strain. This mechanism does not cause the destruction of commensal bacterial flora. Phages are currently being used with success in humans and animals in targeted therapies for slow-healing infections. They have also found application in the US in eliminating pathogens from the surface of foods of animal and plant origin. At a time of growing antibiotic resistance in bacteria and the resulting

  8. Dyslipidemia in HIV Infected Children Receiving Highly Active Antiretroviral Therapy.

    Science.gov (United States)

    Mandal, Anirban; Mukherjee, Aparna; Lakshmy, R; Kabra, Sushil K; Lodha, Rakesh

    2016-03-01

    To assess the prevalence of dyslipidemia and lipodystrophy in Indian children receiving non-nucleoside reverse transcriptase inhibitor (NNRTI) based highly active antiretroviral therapy (HAART) and to determine the associated risk factors for the same. The present cross-sectional study was conducted at a Pediatric Clinic of a tertiary care teaching center in India, from May 2011 through December 2012. HIV infected children aged 5-15 y were enrolled if they did not have any severe disease or hospital admission within last 3 mo or receive any medications known to affect the lipid profile. Eighty-one children were on highly active antiretroviral therapy (HAART) for at least 6 mo and 16 were receiving no antiretroviral therapy (ART). Participants' sociodemographic, nutritional, clinical, and laboratory data were recorded in addition to anthropometry and evidence of lipodystrophy. Fasting lipid profile, apolipoprotein A1 and B levels were done for all the children. Among the children on highly active antiretroviral therapy (HAART), 38.3 % had dyslipidemia and 80.2 % had lipodystrophy, while 25 % antiretroviral therapy (ART) naïve HIV infected children had dyslipidemia. No clinically significant risk factors could be identified that increased the risk of dyslipidemia or lipodystrophy in children on highly active antiretroviral therapy (HAART). There is a high prevalence of dyslipidemia and lipodystrophy in Indian children with HIV infection with an imminent need to establish facilities for testing and treatment of these children for metabolic abnormalities.

  9. Rifaximin therapy for metronidazole-unresponsive Clostridium difficile infection: a prospective pilot trial.

    Science.gov (United States)

    Patrick Basu, P; Dinani, Amreen; Rayapudi, Krishna; Pacana, Tommy; Shah, Niraj James; Hampole, Hemant; Krishnaswamy, N V; Mohan, Vinod

    2010-07-01

    Clostridium difficile infection (CDI) is a recent epidemic in the United States, particularly in the hospital setting. Oral metronidazole is standard therapy for C. difficile infection, but resistance to metronidazole is becoming a clinical challenge. We evaluated the efficacy of the nonsystemic oral antibiotic rifaximin for the treatment of metronidazole-resistant C. difficile infection. Twenty-five patients with C. difficile infection were enrolled in the study. All had mild-to-moderate C. difficile infection (5-10 bowel movements a day without sepsis) unresponsive to metronidazole (i.e. stools positive for toxins A and B after oral metronidazole 500 mg three times daily [t.i.d.] for 5 days). After discontinuation of metronidazole, rifaximin 400 mg t.i.d. for 14 days was prescribed. Patients were followed for 56 days and stool was tested for C. difficile using polymerase chain reaction (PCR) to assess the effect of treatment. A negative PCR test result was interpreted as a favorable response to rifaximin. Sixteen of 22 patients (73%) were eligible for study inclusion and completed rifaximin therapy experienced eradication of infection (stool negative for C. difficile) immediately after rifaximin therapy and 56 days post-treatment. Three patients (12%) discontinued therapy because of abdominal distention. Rifaximin was generally well tolerated. In conclusion, rifaximin may be considered for treatment of mild-to-moderate C. difficile infection that is resistant to metronidazole. Larger randomized trials are needed to confirm these positive findings.

  10. Impact of viral hepatitis co-infection on response to antiretroviral therapy and HIV disease progression in the HIV-NAT cohort

    NARCIS (Netherlands)

    Law, W. Phillip; Duncombe, Chris J.; Mahanontharit, Apicha; Boyd, Mark A.; Ruxrungtham, Kiat; Lange, Joep M. A.; Phanuphak, Praphan; Cooper, David A.; Dore, Gregory J.

    2004-01-01

    OBJECTIVE: To examine the impact of viral hepatitis co-infection on HIV disease outcomes following commencement of combination antiretroviral therapy in a developing country setting. METHODS: HIV RNA suppression, CD4 cell count recovery, and HIV disease progression were examined within a cohort of

  11. Malarial infection among HIV Patients on Antiretroviral Therapy (ART)

    African Journals Online (AJOL)

    Malarial infection among patients on antiretroviral therapy (ART) attending Federal Medical Centre, Makurdi, Benue State was investigated between April and August 2008 to determine the level of malaria infection in HIV/AIDS patients on ART and those not on ART with respect to CD4+ counts, age and gender. A total of ...

  12. Genital condyloma virus infection following pelvic radiation therapy: report of seven cases

    International Nuclear Information System (INIS)

    Lowell, D.M.; Livolsi, V.A.; Ludwig, M.E.

    1983-01-01

    Six women who underwent radiation therapy for gynecologic malignancies demonstrated cytologic evidence of condyloma virus infection 2 or more years following radiation. Histologic confirmation was obtained in two of the cases. A seventh patient developed in situ and invasive squamous cell carcinoma in a vulvar condyloma acuminatum following radiation therapy for Hodgkin's disease. This venereal infection is found most frequently in sexually active younger women (average age, 27 years). It is felt that depressed cell-mediated immunity consequent to the radiation therapy allowed the development of this infection in the older patients described in this report. The evolution of invasive squamous cell carcinoma in the condyloma acuminatum may indicate a possible oncogenic or cocarcinogenic effect of the virus. The immunologic responses to infection caused by the human papillomavirus group are discussed, as well as its potential for malignant transformation

  13. HIV Infection: Advances Toward a Cure.

    Science.gov (United States)

    Douek, Daniel C

    2018-04-01

    Achieving cure of HIV infection requires eliminating all replication-competent virus from the reservoir of latently infected cells or completely inhibiting infected cells from emerging from latency. Strategies include very early use of antiretroviral therapy; hematopoietic stem cell transplantation; "shock-and-kill" approaches; immune therapy with immune checkpoint inhibitors; gene therapy, including use of CC chemokine receptor 5-modified CD4+ T cells; and broadly neutralizing antibody therapy. Success is likely to require a combination of approaches. This article summarizes a presentation by Daniel C. Douek, MD, PhD, at the IAS-USA continuing education program held in Berkeley, California, in May 2017.

  14. THE COMBINED ROLE OF HERBAL THERAPY IN THE PREVENTION OF URINARY TRACT INFECTIONS DURING PROSTATE BIOPSY

    Directory of Open Access Journals (Sweden)

    A. V. Il'yash

    2017-01-01

    Full Text Available Introduction. Prostate biopsy is a routine method for diagnosing prostate cancer. However, there are a number of serious complications associated with this procedure, and especially development of infection.Objective. Evaluation of the effectiveness of complex herbal therapy in the prevention of infectious complications in patients exposed to prostate biopsy.Materials and methods. The study included 40 patients aged 48 to 69 years who underwent prostate biopsy. Patients with chronic prostatitis (category 4 NIH were divided into two groups. Patients in the comparison group limited to standard antibiotic therapy, and the patients of the main group additionally received Canephron N. The efficacy of the therapy was evaluated at 1, 2 and 6 months after the start of treatment by the dynamics of leukocyte count in prostate secretion and bacterial contamination, prostate- specific atigen (PSA level, questionnaire data, ultrasound and urodynamic survey methods.Results. The level of PSA compared to baseline data, decreased by 56.9% in the comparison group and by 67.6% in the main group (p<0.05. A clinically significant bacterial titer and an increase in the number of leukocytes more than10 in sight, were registered in the comparison group in two times more often, than in patients of the main group.Conclusion. The results of the study make it possible to recommend for patients with chronic prostatitis of category 4 NIH the prescription of Canephron N.

  15. Effectiveness and Safety of Immunomodulators with Anti-TNF Therapy in Crohn's Disease

    Science.gov (United States)

    Osterman, Mark T.; Haynes, Kevin; Delzell, Elizabeth; Zhang, Jie; Bewtra, Meenakshi; Brensinger, Colleen M.; Chen, Lang; Xie, Fenglong; Curtis, Jeffrey R.; Lewis, James D.

    2015-01-01

    Background & Aims The benefit of continuing immunomodulators when “stepping up” to anti-tumor necrosis factor (anti-TNF) therapy for Crohn's disease (CD) is uncertain. This study assessed the effectiveness and safety of immunomodulators with anti-TNF therapy in CD. Methods We conducted a retrospective cohort study of new users of anti-TNF therapy for CD in Medicare. Users of anti-TNF combination therapy with immunomodulators were matched to up to 3 users of anti-TNF monotherapy via propensity score and compared using 3 metrics of effectiveness – surgery, hospitalization, and discontinuation of anti-TNF therapy or surgery – and 2 metrics of safety – serious infection and non-Candida opportunistic infection. Cox regression was used for all analyses. Results Among new users of infliximab, we matched 381 users of combination therapy to 912 users of monotherapy; among new users of adalimumab, we matched 196 users of combination therapy to 505 users of monotherapy. Combination therapy occurred predominantly as “step up” after thiopurine therapy. The rates of surgery (hazard ratio [HR] 1.20, 95% CI 0.73-1.96), hospitalization (HR 0.82 [0.57-1.19]), discontinuation of anti-TNF therapy or surgery (HR 1.09, [0.88-1.34]), and serious infection (HR 0.93 [0.88-1.34]) did not differ between users of anti-TNF combination therapy and monotherapy. However, the risk of opportunistic infection (HR 2.64 [1.21-5.73]) and herpes zoster (HR 3.16 [1.25-7.97]) were increased with combination therapy. Conclusions We found that continuation of immunomodulators after “stepping up” to anti-TNF therapy did not improve outcomes but was associated with an increased risk of opportunistic infection. PMID:25724699

  16. Inhaled phage therapy: a promising and challenging approach to treat bacterial respiratory infections.

    Science.gov (United States)

    Bodier-Montagutelli, Elsa; Morello, Eric; L'Hostis, Guillaume; Guillon, Antoine; Dalloneau, Emilie; Respaud, Renaud; Pallaoro, Nikita; Blois, Hélène; Vecellio, Laurent; Gabard, Jérôme; Heuzé-Vourc'h, Nathalie

    2017-08-01

    Bacterial respiratory tract infections (RTIs) are increasingly difficult to treat due to evolving antibiotic resistance. In this context, bacteriophages (or phages) are part of the foreseen alternatives or combination therapies. Delivering phages through the airways seems more relevant to accumulate these natural antibacterial viruses in proximity to their bacterial host, within the infectious site. Areas covered: This review addresses the potential of phage therapy to treat RTIs and discusses preclinical and clinical results of phages administration in this context. Recent phage formulation and aerosolization attempts are also reviewed, raising technical challenges to achieve efficient pulmonary deposition via inhalation. Expert opinion: Overall, the inhalation of phages as antibacterial treatment seems both clinically relevant and technically feasible. Several crucial points still need to be investigated, such as phage product pharmacokinetics and immunogenicity. Furthermore, given phage-specific features, appropriate regulatory and manufacturing guidelines will need to be defined. Finally, randomized controlled clinical trials should be carried out to establish phage therapy's clinical positioning in the antimicrobial arsenal against RTIs.

  17. The clinical impact of immunodeficiency and viraemia in the era of combined antiretroviral therapy for HIV-1 infection

    NARCIS (Netherlands)

    Zhang, S.

    2015-01-01

    Despite treatment with combined antiretroviral therapy (cART), patients may experience viraemia at different levels and for varying periods of time, and CD4 count recovery, even in patients with sustained virus suppression, frequently remains suboptimal. We studied the characteristics of episodes of

  18. Fecal Microbiota Therapy for Clostridium difficile Infection: A Health Technology Assessment.

    Science.gov (United States)

    2016-01-01

    Fecal microbiota therapy is increasingly being used to treat patients with Clostridium difficile infection. This health technology assessment primarily evaluated the effectiveness and cost-effectiveness of fecal microbiota therapy compared with the usual treatment (antibiotic therapy). We performed a literature search using Ovid MEDLINE, Embase, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, CRD Health Technology Assessment Database, Cochrane Central Register of Controlled Trials, and NHS Economic Evaluation Database. For the economic review, we applied economic filters to these search results. We also searched the websites of agencies for other health technology assessments. We conducted a meta-analysis to analyze effectiveness. The quality of the body of evidence for each outcome was examined according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. Using a step-wise, structural methodology, we determined the overall quality to be high, moderate, low, or very low. We used a survey to examine physicians' perception of patients' lived experience, and a modified grounded theory method to analyze information from the survey. For the review of clinical effectiveness, 16 of 1,173 citations met the inclusion criteria. A meta-analysis of two randomized controlled trials found that fecal microbiota therapy significantly improved diarrhea associated with recurrent C. difficile infection versus treatment with vancomycin (relative risk 3.24, 95% confidence interval [CI] 1.85-5.68) (GRADE: moderate). While fecal microbiota therapy is not associated with a significant decrease in mortality compared with antibiotic therapy (relative risk 0.69, 95% CI 0.14-3.39) (GRADE: low), it is associated with a significant increase in adverse events (e.g., short-term diarrhea, relative risk 30.76, 95% CI 4.46-212.44; abdominal cramping, relative risk 14.81, 95% CI 2.07-105.97) (GRADE: low). For

  19. Efficacy of magneto-laser therapy in the treatment of ureaplasma infection

    Directory of Open Access Journals (Sweden)

    N N Aliev

    2018-04-01

    Full Text Available Aim. To study clinical and epidemiological data in males and females with ureaplasma infection and to evaluate efficacy of magneto-laser therapy used as additional treatment of ureaplasma infection. Methods. 104 patients (94 men and 10 women with urogenital ureaplasma infection were observed. Patients were divided into two groups: a study group (n=55 that received standard and magneto-laser therapy, and a comparison group (n=49 that received only standard treatment. Polymerase chain reaction was used to investigate samples for Mycoplasma hominis, Ureaplasma parvum and urealyticum, and bacteriological study for Mycoplasma hominis and Ureaplasma spp. was additionally performed with determining their antibiotic susceptibility. Magnetic therapy was conducted with the use of Michelangelo device (Italy for 10 minutes to small pelvis area for 10 days. Results. As a result, 78 (82.9% males were diagnosed with uretritis, 52 (55.3% with prostatitis, 37 (39.3% with cystitis. In females monoinfection was more prevalent than in males (50.0% vs 40.4%. Ureaplasmosis predominantly affected subjects aged 20-29 (97.8% and 30-39 (86.0% years. In female group, patients aged 20-29 years prevailed, while in a male group - patients aged 30-39 years. In males, the association of Ureaplasma with Mycoplasma hominis (36.1% prevailed. Conclusion. Complex treatment of ureaplasma infection of urogenital tract including magneto-laser therapy demonstrated high clinical efficacy and allowed achieving clinical and laboratory cure of ureaplasma infection in 85.4% of cases.

  20. Successful treatment of methicillin-resistant Staphylococcus aureus osteomyelitis with combination therapy using linezolid and rifampicin under therapeutic drug monitoring.

    Science.gov (United States)

    Ashizawa, Nobuyuki; Tsuji, Yasuhiro; Kawago, Koyomi; Higashi, Yoshitsugu; Tashiro, Masato; Nogami, Makiko; Gejo, Ryuichi; Narukawa, Munetoshi; Kimura, Tomoatsu; Yamamoto, Yoshihiro

    2016-05-01

    Linezolid is an effective antibiotic against most gram-positive bacteria including drug-resistant strains such as methicillin-resistant Staphylococcus aureus. Although linezolid therapy is known to result in thrombocytopenia, dosage adjustment or therapeutic drug monitoring of linezolid is not generally necessary. In this report, however, we describe the case of a 79-year-old woman with recurrent methicillin-resistant S. aureus osteomyelitis that was successfully treated via surgery and combination therapy using linezolid and rifampicin under therapeutic drug monitoring for maintaining an appropriate serum linezolid concentration. The patient underwent surgery for the removal of the artificial left knee joint and placement of vancomycin-impregnated bone cement beads against methicillin-resistant S. aureus after total left knee implant arthroplasty for osteoarthritis. We also initiated linezolid administration at a conventional dose of 600 mg/h at 12-h intervals, but reduced it to 300 mg/h at 12-h intervals on day 9 because of a decrease in platelet count and an increase in serum linezolid trough concentration. However, when the infection exacerbated, we again increased the linezolid dose to 600 mg/h at 12-h intervals and performed combination therapy with rifampicin, considering their synergistic effects and the control of serum linezolid trough concentration via drug interaction. Methicillin-resistant S. aureus infection improved without reducing the dose of or discontinuing linezolid. The findings in the present case suggest that therapeutic drug monitoring could be useful for ensuring the therapeutic efficacy and safety of combination therapy even in patients with osteomyelitis who require long-term antibiotic administration. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  1. Era of liver transplantation: combined anatomic splenectomy and anticoagulant therapy in prevention of portal vein thrombosis after splenectomy.

    Science.gov (United States)

    Hongwei, Chen; Zhang, Liang; Maoping, Li; Yong, Zhang; Chengyou, Du; Dewei, Li

    2015-01-01

    Portal vein thrombosis (PVT) is a common complication following splenectomy in patients with liver cirrhosis and portal hypertension, which also brings difficulties to future possible liver transplantation. This paper retrospectively analyzes the preventive effect of combined anatomic splenectomy and early anticoagulant therapy on post-splenectomy portal vein thrombosis in patients with portal hypertension. We retrospectively analyzed 136 patients who underwent splenectomy at our hospital between January 2010 and December 2013 due to liver cirrhosis and portal hypertension. Patient conditions, such as coagulation function, splenic and portal vein thrombosis, intra-abdominal hemorrhage, pancreatic leakage and intra-abdominal infections, are observed postoperatively. Despite the presence of liver cirrhosis and portal hypertension in patients, early postoperative anticoagulant therapy has no significant impact on coagulation function and intra-abdominal hemorrhage of these patients (p > 0.05). Anatomic splenectomy can reduce the occurrence of complications such as postoperative bleeding, pancreatic leakage and intra-abdominal infections (p splenectomy and early postoperative anticoagulant therapy can reduce post-splenectomy portal vein thrombosis in patients with portal hypertension, and is conducive to the future liver transplantation therapy may be needed by the patients.

  2. [Influence of Saccharomyces boulardii Sachets combined with bismuth quadruple therapy for initial Helicobacter pylori eradication].

    Science.gov (United States)

    Zhu, X Y; Du, J; Wu, J; Zhao, L W; Meng, X; Liu, G F

    2017-08-08

    Objective: To evaluate the efficacy and safety of Saccharomyces boulardii Sachets combined with bismuth quadruple therapy for initial Helicobacter pylori ( H . pylori ) eradication. Methods: From March 2014 to March 2015, 240 participants from the third hospital of Hebei medical university with H . pylori infection were recruited and randomized into three groups: Quadruple therapy group received bismuth potassium citrate 220 mg bid + Rabeprazole 10 mg bid + amoxicillin 1 000 mg bid+ furazolidone 100 mg bid for 10 days. Short-term group and long-term group received the same quadruple therapy for 10 days as above, as well as Saccharomyces boulardii Sachets 500 mg bid for 14 days and 28 days, respectively. H . pylori eradication was confirmed by (13)C/(14)C-UBT at least 4 weeks after completion of therapy. And side effects were investigated during the therapy. Results: The H . pylori eradication rates in quadruple therapy, short-term and long-term group were 80%, 87.5% and 87.5% by ITT analysis ( P =0.321) and 92.8%, 94.6% and 95.9% by PP analysis ( P =0.717), respectively. The overall side effect rate and occurrence of diarrhea and abdominal distension were significantly lower in short-term or long-term group as compared with quadruple therapy group( P =0.007, 0.003, 0.004), but there was no significant difference between the two probiotics groups. Conclusions: Both short and long-term Saccharomyces boulardii Sachets reduced the overall side effect rate and occurrence of diarrhea or abdominal distension when combined with bismuth quadruple therapy for initial H . pylori eradication and no difference was observed in efficacy or safety between the two groups.

  3. Nanomedicine-based combination anticancer therapy between nucleic acids and small-molecular drugs.

    Science.gov (United States)

    Huang, Wei; Chen, Liqing; Kang, Lin; Jin, Mingji; Sun, Ping; Xin, Xin; Gao, Zhonggao; Bae, You Han

    2017-06-01

    Anticancer therapy has always been a vital challenge for the development of nanomedicine. Repeated single therapeutic agent may lead to undesirable and severe side effects, unbearable toxicity and multidrug resistance due to complex nature of tumor. Nanomedicine-based combination anticancer therapy can synergistically improve antitumor outcomes through multiple-target therapy, decreasing the dose of each therapeutic agent and reducing side effects. There are versatile combinational anticancer strategies such as chemotherapeutic combination, nucleic acid-based co-delivery, intrinsic sensitive and extrinsic stimulus combinational patterns. Based on these combination strategies, various nanocarriers and drug delivery systems were engineered to carry out the efficient co-delivery of combined therapeutic agents for combination anticancer therapy. This review focused on illustrating nanomedicine-based combination anticancer therapy between nucleic acids and small-molecular drugs for synergistically improving anticancer efficacy. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Risks and safety of combination therapy for hypothyroidism.

    Science.gov (United States)

    Jonklaas, Jacqueline

    2016-08-01

    Hypothyroidism is currently a condition that can be treated, but not cured. Although levothyroxine reverses stigmata of hypothyroidism in most individuals, some patients feel dissatisfied with 'monotherapy', and this has stimulated interest in 'combination therapy' with both levothyroxine and liothyronine. A search of PubMed was conducted using terms including hypothyroidism, treatment, benefits, risks, and safety. Based on the articles identified, the body of evidence regarding the efficacy of traditional levothyroxine is reviewed. Concerns with levothyroxine therapy including impaired quality of life in treated patients, thyroxine-predominant hormone ratios, and inadvertent iatrogenic thyroid disease are discussed. The trials of combination therapy performed since 1999 were reviewed. The heterogeneity of these trials, both in terms of design and results, is discussed. The potential for new trials to determine whether combination therapy can reverse the dissatisfaction associated with monotherapy, while avoiding non-physiologic hormone ratios, inadvertent thyrotoxicosis, and unacceptable side effects is discussed. Expert commentary: Research regarding which therapy fully reverses hypothyroidism at a tissue and cellular level is ongoing. The field would be advanced by the development of an extended release preparation of liothyronine. In the future regeneration of functional thyroid follicles from stem cells may offer hope for curing hypothyroidism.

  5. Emerging therapies for Clostridium difficile infection – focus on fidaxomicin

    Directory of Open Access Journals (Sweden)

    Chaparro-Rojas F

    2013-06-01

    Full Text Available Fredy Chaparro-Rojas, Kathleen M MullaneDepartment of Medicine, Section of Infectious Diseases, University of Chicago, Chicago, IL, USAAbstract: The epidemiology of Clostridium difficile infections (CDI has evolved during the last decades, with an increase in the reported incidence, severity of cases, and rate of mortality and relapses. These increases have primarily affected some special populations including the elderly, patients requiring concomitant antibiotic therapy, patients with renal failure, and patients with cancer. Until recently, the treatment of CDI was limited to either metronidazole or vancomycin. New therapeutic options have emerged to address the shortcomings of current antibiotic therapy. Fidaxomicin stands out as the first-in-class oral macrocyclic antibiotic with targeted activity against C. difficile and minimal collateral damage on the normal colonic flora. Fidaxomicin has demonstrated performance not inferior to what is considered the “gold standard” available therapy for CDI, vancomycin, in two separate Phase III clinical trials, but with significant advantages, including fewer recurrences and higher rates of sustained clinical cures. Fidaxomicin constitutes an important development in targeted antibiotic therapy for CDI and must be considered as a first-line agent for patients with risk factors known to portend relapse and severe infection.Keywords: fidaxomicin, Clostridium difficile-associated diarrhea, CDAD, Clostridium difficile infection (CDI, vancomycin, metronidazole

  6. Antiretroviral therapy during pregnancy and the risk of an adverse outcome.

    Science.gov (United States)

    Tuomala, Ruth E; Shapiro, David E; Mofenson, Lynne M; Bryson, Yvonne; Culnane, Mary; Hughes, Michael D; O'Sullivan, M J; Scott, Gwendolyn; Stek, Alice M; Wara, Diane; Bulterys, Marc

    2002-06-13

    Some studies suggest that combination antiretroviral therapy in pregnant women with human immunodeficiency virus type 1 (HIV-1) infection increases the risk of premature birth and other adverse outcomes of pregnancy. We studied pregnant women with HIV-1 infection who were enrolled in seven clinical studies and delivered their infants from 1990 through 1998. The cohort comprised 2123 women who received antiretroviral therapy during pregnancy (monotherapy in 1590, combination therapy without protease inhibitors in 396, and combination therapy with protease inhibitors in 137) and 1143 women who did not receive antiretroviral therapy. After standardization for the CD4+ cell count and use or nonuse of tobacco, alcohol, and illicit drugs, the rate of premature delivery (women who received antiretroviral therapy and those who did not (16 percent and 17 percent, respectively); the rate of low birth weight (women who received combination therapy with protease inhibitors (5 percent) had infants with very low birth weight, as compared with nine women who received combination therapy without protease inhibitors (2 percent) (adjusted odds ratio, 3.56; 95 percent confidence interval, 1.04 to 12.19). As compared with no antiretroviral therapy or monotherapy, combination therapy for HIV-1 infection in pregnant women is not associated with increased rates of premature delivery or with low birth weight, low Apgar scores, or stillbirth in their infants. The association between combination therapy with protease inhibitors and an increased risk of very low birth weight requires confirmation.

  7. Antibiotic therapy for preventing infections in people with acute stroke

    NARCIS (Netherlands)

    Vermeij, Jan-Dirk; Westendorp, Willeke F.; Dippel, Diederik Wj; van de Beek, Diederik; Nederkoorn, Paul J.

    2018-01-01

    Stroke is the main cause of disability in high-income countries and ranks second as a cause of death worldwide. Infections occur frequently after stroke and may adversely affect outcome. Preventive antibiotic therapy in the acute phase of stroke may reduce the incidence of infections and improve

  8. Antibiotic therapy for preventing infections in patients with acute stroke

    NARCIS (Netherlands)

    Westendorp, Willeke F.; Vermeij, Jan-Dirk; Vermeij, Frederique; den Hertog, Heleen M.; Dippel, Diederik W. J.; van de Beek, Diederik; Nederkoorn, Paul J.

    2012-01-01

    Background Stroke is the main cause of disability in high income countries and ranks second as a cause of death worldwide. Infections occur frequently after stroke and may adversely affect outcome. Preventive antibiotic therapy in the acute phase of stroke may reduce infections and improve outcome.

  9. Improvement of therapy for escherichiosis in children infected with Epstein-Barr virus

    Directory of Open Access Journals (Sweden)

    Ye.S. Olkhovskyy

    2017-03-01

    Full Text Available Background. Escherichiosis remains one of the most common intestinal infections, especially among young children. Indigestion of essential nutrients, transient fermentopathy, imbalance of the symbiotic flora, which develop in escherichiosis in combination with general intoxication and water-electrolyte disturbances, can lead to unfavorable outcomes. One of the factors influencing the course of escherichiosis can be Epstein-Barr virus (EBV infection in the child. Purpose of the research — improvement of treatment of children with escherichiosis and EBV infection in different periods of the disease. Materials and methods. We examined 74 children aged 2–3 years, who were treated at the Regional Children’s Clinical Infectious Diseases Hospital in Kharkiv with a diagnosis of moderate-to-severe escherichiosis. A group of 36 children was selected, who received conventional therapy with early gradual restoration of nutrition according to the existing protocol, and the restoration of the qualitative and quantitative composition of food was carried out as soon as possible (first group. The second group was represented by 38 children, who received two-day prolonged gradual restoration of the diet: more gradual increasing the volume of food at each feeding and reducing the number of feedings per day. Children of the second group received drugs containing Lactobacillus, milk thistle extract and B vitamins (once daily with meals from the first day. Ultrasound examination of the abdominal cavity was performed in all children. Results. Analysis of the main clinical, laboratory and instrumental parameters of patients in both groups during their stay in the hospital and one month after the discharge from the hospital revealed that in children of the second group, in whom rational diet therapy was applied, there was a reduction in the duration of bowel dysfunction, abdominal syndrome, flatulence; the parameters of the coprological test and the echosonoscopy

  10. Fecal Microbiota Therapy for Clostridium difficile Infection: A Health Technology Assessment

    Science.gov (United States)

    2016-01-01

    Background Fecal microbiota therapy is increasingly being used to treat patients with Clostridium difficile infection. This health technology assessment primarily evaluated the effectiveness and cost-effectiveness of fecal microbiota therapy compared with the usual treatment (antibiotic therapy). Methods We performed a literature search using Ovid MEDLINE, Embase, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, CRD Health Technology Assessment Database, Cochrane Central Register of Controlled Trials, and NHS Economic Evaluation Database. For the economic review, we applied economic filters to these search results. We also searched the websites of agencies for other health technology assessments. We conducted a meta-analysis to analyze effectiveness. The quality of the body of evidence for each outcome was examined according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. Using a step-wise, structural methodology, we determined the overall quality to be high, moderate, low, or very low. We used a survey to examine physicians’ perception of patients’ lived experience, and a modified grounded theory method to analyze information from the survey. Results For the review of clinical effectiveness, 16 of 1,173 citations met the inclusion criteria. A meta-analysis of two randomized controlled trials found that fecal microbiota therapy significantly improved diarrhea associated with recurrent C. difficile infection versus treatment with vancomycin (relative risk 3.24, 95% confidence interval [CI] 1.85–5.68) (GRADE: moderate). While fecal microbiota therapy is not associated with a significant decrease in mortality compared with antibiotic therapy (relative risk 0.69, 95% CI 0.14–3.39) (GRADE: low), it is associated with a significant increase in adverse events (e.g., short-term diarrhea, relative risk 30.76, 95% CI 4.46–212.44; abdominal cramping, relative risk 14

  11. The Prospect of Immunoglobulin Y for Therapy of Canine parvovirus Infection in Dogs

    Directory of Open Access Journals (Sweden)

    I Gusti Ayu Agung Suartini

    2015-06-01

    Full Text Available Canine parvovirus (CPV is a highly infectious virus. The virus causes death in dogs worldwide. The mortality rate due to infection of CPV in dog reaches 91%. Prevention of CPV infection in puppies has been done by vaccination which is effectively proven. Protective mechanisms of maternal antibodies contribute to the failure of vaccination. Highly stable characteristics of parvovirus enable the virus still exist in the environment. Various therapies are performed only to suppress the clinical symptoms but can not reduce puppy mortalities. This review discusses CPV alternative therapy and the advantages using immunoglobulin Y (IgY specific antibodies isolated from chicken egg yolk. Immunoglobulin Y will neutralize the virus, so it can not infect host cells. Intravenous IgY therapy has shown to suppress the spread of CPV infection and prevent death.

  12. Triple therapy in COPD: new evidence with the extrafine fixed combination of beclomethasone dipropionate, formoterol fumarate, and glycopyrronium bromide

    Directory of Open Access Journals (Sweden)

    Singh D

    2017-10-01

    Full Text Available Dave Singh,1 Massimo Corradi,2 Monica Spinola,3 Alberto Papi,4 Omar S Usmani,5 Mario Scuri,3 Stefano Petruzzelli,3 Jørgen Vestbo1 1Division of Infection, Immunity and Respiratory Medicine, University of Manchester, Manchester, UK; 2Department of Medicine and Surgery, University of Parma, Parma, Italy; 3Chiesi Farmaceutici SpA, Parma, Italy; 4Department of Medical Sciences, Research Centre on Asthma and COPD, University of Ferrara, Ferrara, Italy; 5National Heart and Lung Institute, Imperial College London, London, UK Abstract: The goals of COPD therapy are to prevent and control symptoms, reduce the frequency and severity of exacerbations, and improve exercise tolerance. The triple combination therapy of inhaled corticosteroids (ICSs, long-acting beta2 agonists (LABAs, and long-acting muscarinic antagonists (LAMAs has become an option for maintenance treatment of COPD and as a “step-up” therapy from single or double combination treatments. There is evidence that triple combination ICS/LABA/LAMA with different inhalers improves lung function, symptoms, and health status and reduces exacerbations. A new triple fixed-dose combination of extrafine beclomethasone dipropionate (100 µg/puff/formoterol fumarate (6 µg/puff/glycopyrronium bromide (12.5 µg/puff has been developed as a hydrofluoroalkane pressurized metered dose inhaler. Two large pivotal studies showed that this extrafine fixed ICS/LABA/LAMA triple combination is superior to fixed ICS/LABA combined therapy and also superior to the LAMA tiotropium in terms of lung function and exacerbation prevention in COPD patients at risk of exacerbation. This review considers the new information provided by these clinical trials of extrafine triple therapy and the implications for the clinical management of COPD patients. Keywords: COPD, inhaled triple therapy, beclomethasone dipropionate, formoterol fumarate and glycopyrronium bromide

  13. Combination of α-glucosidase inhibitor and ribavirin for the treatment of dengue virus infection in vitro and in vivo.

    Science.gov (United States)

    Chang, Jinhong; Schul, Wouter; Butters, Terry D; Yip, Andy; Liu, Boping; Goh, Anne; Lakshminarayana, Suresh B; Alonzi, Dominic; Reinkensmeier, Gabriele; Pan, Xiaoben; Qu, Xiaowang; Weidner, Jessica M; Wang, Lijuan; Yu, Wenquan; Borune, Nigel; Kinch, Mark A; Rayahin, Jamie E; Moriarty, Robert; Xu, Xiaodong; Shi, Pei-Yong; Guo, Ju-Tao; Block, Timothy M

    2011-01-01

    Cellular α-glucosidases I and II are enzymes that sequentially trim the three terminal glucoses in the N-linked oligosaccharides of viral envelope glycoproteins. This process is essential for the proper folding of viral glycoproteins and subsequent assembly of many enveloped viruses, including dengue virus (DENV). Imino sugars are substrate mimics of α-glucosidases I and II. In this report, we show that two oxygenated alkyl imino sugar derivatives, CM-9-78 and CM-10-18, are potent inhibitors of both α-glucosidases I and II in vitro and in treated animals, and efficiently inhibit DENV infection of cultured human cells. Pharmacokinetic studies reveal that both compounds are well tolerated at doses up to 100mg/kg in rats and have favorable pharmacokinetic properties and bioavailability in mice. Moreover, we showed that oral administration of either CM-9-78 or CM-10-18 reduces the peak viremia of DENV in mice. Interestingly, while treatment of DENV infected mice with ribavirin alone did not reduce the viremia, combination therapy of ribavirin with sub-effective dose of CM-10-18 demonstrated a significantly enhanced antiviral activity, as indicated by a profound reduction of the viremia. Our findings thus suggest that combination therapy of two broad-spectrum antiviral agents may provide a practically useful approach for the treatment of DENV infection. Copyright © 2010 Elsevier B.V. All rights reserved.

  14. Combination of alpha-glucosidase inhibitor and ribavirin for the treatment of Dengue virus infection in vitro and in vivo

    Science.gov (United States)

    Chang, Jinhong; Schul, Wouter; Butters, Terry D.; Yip, Andy; Liu, Boping; Goh, Anne; Lakshminarayana, Suresh B.; Alonzi, Dominic; Reinkensmeier, Gabriele; Pan, Xiaoben; Qu, Xiaowang; Weidner, Jessica M.; Wang, Lijuan; Yu, Wenquan; Borune, Nigel; Kinch, Mark A.; Rayahin, Jamie E.; Moriarty, Robert; Xu, Xiaodong; Shi, Pei-Yong; Guo, Ju-Tao; Block, Timothy M.

    2010-01-01

    Cellular α-glucosidases I and II are enzymes that sequentially trim the three terminal glucoses in the N-linked oligosaccharides of viral envelope glycoproteins. This process is essential for the proper folding of viral glycoproteins and subsequent assembly of many enveloped viruses, including dengue virus (DENV). Imino sugars are substrate mimics of α-glucosidases I and II. In this report, we show that two oxygenated alkyl imino sugar derivatives, CM-9-78 and CM-10-18, are potent inhibitors of both α-glucosidases I and II in vitro and in treated animals, and efficiently inhibit DENV infection of cultured human cells. Pharmacokinetic studies reveal that both compounds are well tolerated at doses up to 100mg/kg in rats and have favorable pharmacokinetic properties and bioavailability in mice. Moreover, we showed that oral administration of either CM-9-78 or CM-10-18 reduces the peak viremia of DENV in mice. Interestingly, while treatment of DENV infected mice with ribavirin alone did not reduce the viremia, combination therapy of ribavirin with sub-effective dose of CM-10-18 demonstrated a significantly enhanced antiviral activity, as indicated by a profound reduction of the viremia. Our findings thus suggest that combination therapy of two broad-spectrum antiviral agents may provide a practically useful approach for the treatment of DENV infection. PMID:21073903

  15. Combined statin-fibrate therapy-induced rhabdomyolysis: Case report

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    Jozić Tanja L.

    2014-01-01

    Full Text Available Introduction Rhabdomyolysis is a rare, but serious and potentially fatal adverse reaction of the statin application that may be developed in any time of therapy. It is characterized by massive destruction of muscles associated with the large increase of creatine kinase (CK leading to myoglobinuria and potential acute renal failure. Combined statin-fibrate therapy increases the risk of rhabdomyolysis, especially in elderly and diabetic patients. Case report An 81-year-old male was admitted to Coronary Care Unit of the Emergency Center, Clinical Center of Serbia (CCS with the clinical picture and electrocardiogram of the acute anterior wall myocardial infarction complicated with pulmonary edema. Laboratory tests on admission showed higher elevated values of serum creatinine 179 μmol/L and BUN 9.2 mmol/L (eGFR 32 mL/min/1.73m2, CK 309 U/L (on day 2: 3476 U/L and mixed hyperlipidemia (total cholesterol 10.3 mmol/L, HDL 2.26 mmol/L, TG 4.85 mmol/L. The patient was treated with thrombolysis medication therapy (Alteplase, anticoagulant and dual antiplatelet therapy, diuretics, organic nitrates, angiotensin-converting enzyme (ACE inhibitors, antibiotics, and proton pump inhibitors. During seven days, his therapy included combined pravastatin 20 mg and fenofibrate (160 mg, which was discontinued due to pains and weakness of muscles and significantly elevated CC to 7080 U/L (upper limit 200 U/L, but no significant deterioration of renal function was observed. Discontinuation of therapy resulted in CC level normalization and improvement of clinical condition. Conclusion Combined statin and fibrate therapy requires strict clinical control and monitoring of CK i transaminases. Four-time or higher increase of CK requires discontinuation of therapy. In addition, patients are advised to report immediately any pains in muscles, sensibility, weakness or cramps.

  16. HIV infection and treatment: beyond viral control

    NARCIS (Netherlands)

    Sprenger, Herman

    2017-01-01

    Since 1996, Infection caused by the human immunodeficiency virus(HIV) can be successfully treated with a combination therapy of 3 antiviral drugs from 2 different classes. Life expectancy has increased dramatically by this treatment. Especially in the early years these combination therapies had many

  17. Overcoming tumor resistance by heterologous adeno-poxvirus combination therapy

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    Markus Vähä-Koskela

    2014-01-01

    Full Text Available Successful cancer control relies on overcoming resistance to cell death and on activation of host antitumor immunity. Oncolytic viruses are particularly attractive in this regard, as they lyse infected tumor cells and trigger robust immune responses during the infection. However, repeated injections of the same virus promote antiviral rather than antitumor immunity and tumors may mount innate antiviral defenses to restrict oncolytic virus replication. In this article, we have explored if alternating the therapy virus could circumvent these problems. We demonstrate in two virus-resistant animal models a substantial delay in antiviral immune- and innate cellular response induction by alternating injections of two immunologically distinct oncolytic viruses, adenovirus, and vaccinia virus. Our results are in support of clinical development of heterologous adeno-/vaccinia virus therapy of cancer.

  18. Combining Oncolytic Virotherapy with p53 Tumor Suppressor Gene Therapy

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    Christian Bressy

    2017-06-01

    Full Text Available Oncolytic virus (OV therapy utilizes replication-competent viruses to kill cancer cells, leaving non-malignant cells unharmed. With the first U.S. Food and Drug Administration-approved OV, dozens of clinical trials ongoing, and an abundance of translational research in the field, OV therapy is poised to be one of the leading treatments for cancer. A number of recombinant OVs expressing a transgene for p53 (TP53 or another p53 family member (TP63 or TP73 were engineered with the goal of generating more potent OVs that function synergistically with host immunity and/or other therapies to reduce or eliminate tumor burden. Such transgenes have proven effective at improving OV therapies, and basic research has shown mechanisms of p53-mediated enhancement of OV therapy, provided optimized p53 transgenes, explored drug-OV combinational treatments, and challenged canonical roles for p53 in virus-host interactions and tumor suppression. This review summarizes studies combining p53 gene therapy with replication-competent OV therapy, reviews preclinical and clinical studies with replication-deficient gene therapy vectors expressing p53 transgene, examines how wild-type p53 and p53 modifications affect OV replication and anti-tumor effects of OV therapy, and explores future directions for rational design of OV therapy combined with p53 gene therapy.

  19. Gleaning Insights from Fecal Microbiota Transplantation and Probiotic Studies for the Rational Design of Combination Microbial Therapies

    Science.gov (United States)

    Hudson, Lauren E.; Anderson, Sarah E.; Corbett, Anita H.

    2016-01-01

    SUMMARY Beneficial microorganisms hold promise for the treatment of numerous gastrointestinal diseases. The transfer of whole microbiota via fecal transplantation has already been shown to ameliorate the severity of diseases such as Clostridium difficile infection, inflammatory bowel disease, and others. However, the exact mechanisms of fecal microbiota transplant efficacy and the particular strains conferring this benefit are still unclear. Rationally designed combinations of microbial preparations may enable more efficient and effective treatment approaches tailored to particular diseases. Here we use an infectious disease, C. difficile infection, and an inflammatory disorder, the inflammatory bowel disease ulcerative colitis, as examples to facilitate the discussion of how microbial therapy might be rationally designed for specific gastrointestinal diseases. Fecal microbiota transplantation has already shown some efficacy in the treatment of both these disorders; detailed comparisons of studies evaluating commensal and probiotic organisms in the context of these disparate gastrointestinal diseases may shed light on potential protective mechanisms and elucidate how future microbial therapies can be tailored to particular diseases. PMID:27856521

  20. Combined therapy of interleukin-12 and interleukin-18 against cryptococcus neoformans infection in a murine model

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Objective To explore adverse effects of combined treatment of interleukin-12 (IL-12) and interleukin-18 (IL-18) against cryptococcosis in a murine model.Methods Infected mice were treated with a combination of IL-12 and IL-18. Their body weight and intake of water and food were observed and recorded. Serum levels of leptin were detected with an enzyme-linked immuno sorbent assay (ELISA).Results In the combined treatment group, the intake volume of water and food were reduced, leading to weight loss and undetectable levels of leptin in the serum. These adverse effects were more profound in mice that had received higher doses of cytokines, which sometimes led to a fatal outcome. There was a significant difference compared with the control group. Neutralization of endogenous tumor necrosis factor-α (TNF-α) by its specific mAb did not alter the wasting effect of this treatment.Conclusions The combined IL-12/IL-18 treatment may cause a number of adverse effects independent of TNF-α and leptin synthesis. Further investigations for resolving these adverse effects are required before clinical application of these cytokines.

  1. Effectiveness of Manual Therapy Combined With Physical Therapy in Treatment of Patellofemoral Pain Syndrome: Systematic Review.

    Science.gov (United States)

    Espí-López, Gemma Victoria; Arnal-Gómez, Anna; Balasch-Bernat, Mercè; Inglés, Marta

    2017-06-01

    The purpose of this study was to conduct a review of randomized controlled trials (RCTs) to determine the treatment effectiveness of the combination of manual therapy (MT) with other physical therapy techniques. Systematic searches of scientific literature were undertaken on PubMed and the Cochrane Library (2004-2014). The following terms were used: "patellofemoral pain syndrome," "physical therapy," "manual therapy," and "manipulation." RCTs that studied adults diagnosed with patellofemoral pain syndrome (PFPS) treated by MT and physical therapy approaches were included. The quality of the studies was assessed by the Jadad Scale. Five RCTs with an acceptable methodological quality (Jadad ≥ 3) were selected. The studies indicated that MT combined with physical therapy has some effect on reducing pain and improving function in PFPS, especially when applied on the full kinetic chain and when strengthening hip and knee muscles. The different combinations of MT and physical therapy programs analyzed in this review suggest that giving more emphasis to proximal stabilization and full kinetic chain treatments in PFPS will help better alleviation of symptoms.

  2. Betamethasone augments the antifungal effect of menadione--towards a novel anti-Candida albicans combination therapy.

    Science.gov (United States)

    Jakab, Ágnes; Emri, Tamás; Sipos, Lilla; Kiss, Ágnes; Kovács, Renátó; Dombrádi, Viktor; Kemény-Beke, Ádám; Balla, József; Majoros, László; Pócsi, István

    2015-08-01

    The fluorinated glucocorticoid betamethasone stimulated both the extracellular phospholipase production and hypha formation of the opportunistic human pathogen Candida albicans and also decreased the efficiency of the polyene antimycotics amphotericin B and nystatin against C. albicans in a dose-dependent manner. Importantly, betamethasone increased synergistically the anti-Candida activity of the oxidative stress generating agent menadione, which may be exploited in future combination therapies to prevent or cure C. albicans infections, in the field of dermatology. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. ROLE OF ENTEROSORPTION IN COMPREHENSIVE THERAPY FOR ACUTE RESPIRATORY DISEASES COMBINED DAMAGE TO WITH GASTROINTESTINAL TRACT DISEASE

    Directory of Open Access Journals (Sweden)

    Yu.B. Belan

    2010-01-01

    Full Text Available The frequency of acute respiratory infections remains high in childhood. It is impossible to identify etiology most accurately in each particular case. However, according to multiple studies, viruses, their associations with each other and bacteria prevail as causative agents. In addition, it is quite often that a respiratory infection, especially in minor children, is combined with a condition of the gastrointestinal tract. Apart from symptomatic and antiviral therapies in these cases, as the authors of this article demonstrated, it is advisable to use enterosorbents. This tactics results in a decreased level of intoxication, lower intensity and duration of diarrheal syndrome, i.e. more speedy recovery.Key words: acute respiratory infections, condition of gastro tract, intoxication, diarrheal syndrome, treatment, enterosorbents, children. (Pediatric Pharmacology. – 2010; 7(3:88-90

  4. A Rapid Screening Assay Identifies Monotherapy with Interferon-ß and Combination Therapies with Nucleoside Analogs as Effective Inhibitors of Ebola Virus.

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    Stephen D S McCarthy

    2016-01-01

    Full Text Available To date there are no approved antiviral drugs for the treatment of Ebola virus disease (EVD. While a number of candidate drugs have shown limited efficacy in vitro and/or in non-human primate studies, differences in experimental methodologies make it difficult to compare their therapeutic effectiveness. Using an in vitro model of Ebola Zaire replication with transcription-competent virus like particles (trVLPs, requiring only level 2 biosafety containment, we compared the activities of the type I interferons (IFNs IFN-α and IFN-ß, a panel of viral polymerase inhibitors (lamivudine (3TC, zidovudine (AZT tenofovir (TFV, favipiravir (FPV, the active metabolite of brincidofovir, cidofovir (CDF, and the estrogen receptor modulator, toremifene (TOR, in inhibiting viral replication in dose-response and time course studies. We also tested 28 two- and 56 three-drug combinations against Ebola replication. IFN-α and IFN-ß inhibited viral replication 24 hours post-infection (IC50 0.038μM and 0.016μM, respectively. 3TC, AZT and TFV inhibited Ebola replication when used alone (50-62% or in combination (87%. They exhibited lower IC50 (0.98-6.2μM compared with FPV (36.8μM, when administered 24 hours post-infection. Unexpectedly, CDF had a narrow therapeutic window (6.25-25μM. When dosed >50μM, CDF treatment enhanced viral infection. IFN-ß exhibited strong synergy with 3TC (97.3% inhibition or in triple combination with 3TC and AZT (95.8% inhibition. This study demonstrates that IFNs and viral polymerase inhibitors may have utility in EVD. We identified several 2 and 3 drug combinations with strong anti-Ebola activity, confirmed in studies using fully infectious ZEBOV, providing a rationale for testing combination therapies in animal models of lethal Ebola challenge. These studies open up new possibilities for novel therapeutic options, in particular combination therapies, which could prevent and treat Ebola infection and potentially reduce drug

  5. KIR-HLA genotypes in HIV-infected patients lacking immunological recovery despite effective antiretroviral therapy.

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    Alessandro Soria

    Full Text Available BACKGROUND: In HIV-infected individuals, mechanisms underlying unsatisfactory immune recovery during effective combination antiretroviral therapy (cART have yet to be fully understood. We investigated whether polymorphism of genes encoding immune-regulating molecules, such as killer immunoglobulin-like receptors (KIR and their ligands class I human leukocyte antigen (HLA, could influence immunological response to cART. METHODS: KIR and HLA frequencies were analyzed in 154 HIV-infected and cART-treated patients with undetectable viral load divided into two groups: 'immunological non responders' (INR, N = 50, CD4(+ T-cell count 350/mm(3. Molecular KIR were typed using polymerase chain reaction-based genotyping. Comparisons were adjusted for baseline patient characteristics. RESULTS: The frequency of KIR2DL3 allele was significantly higher in FR than in INR (83.7% vs. 62%, P = 0.005. The functional compound genotype HLA-C1(+/KIR2DL3(+, even at multivariable analysis, when adjusted for nadir CD4(+ T-cell count, was associated with reduced risk of INR status: odds ratio (95% Confidence Intervals 0.34 (0.13-0.88, P = 0.03. CONCLUSIONS: Reduced presence of the inhibitory KIR2DL3 genotype detected in INR might provoke an imbalance in NK function, possibly leading to increased immune activation, impaired killing of latently infected cells, and higher proviral burden. These factors would hinder full immune recovery during therapy.

  6. Adrenomedullin and angiopoietin-1 additively restore erectile function in diabetic rats: comparison with the combination therapy of vascular endothelial growth factor and angiopoietin-1.

    Science.gov (United States)

    Nishimatsu, Hiroaki; Suzuki, Etsu; Nomiya, Akira; Niimi, Aya; Suzuki, Motofumi; Fujimura, Tetsuya; Fukuhara, Hiroshi; Homma, Yukio

    2013-07-01

    Erectile dysfunction (ED) is a major health problem. We have shown that adrenomedullin (AM) restores erectile function in diabetic rats. The aim of this study is to explore a better treatment for ED, we examined whether combination of AM and angiopoietin-1 (Ang-1) was more effective to treat ED than treatment with AM alone or Ang-1 alone. We also compared the effect of the combination therapy with that of treatment with vascular endothelial growth factor-A (VEGF-A). Male Wistar rats were injected with streptozotocin (STZ) to induce diabetes. Adenoviruses expressing AM (AdAM), Ang-1 (AdAng-1), and VEGF-A (AdVEGF-A) were injected into the penis 6 weeks after STZ administration. Erectile function, penile histology, and protein expression were analyzed 4 weeks after the injection of the adenoviruses. Intracavernous pressure and mean arterial pressure were measured to evaluate erectile function. The morphology of the penis was analyzed by Elastica van Gieson stain and immunohistochemistry. The expression of α-smooth muscle actin (SMA), VE-cadherin and type I collagen was assessed by Western blot analysis. Infection with AdAM plus AdAng-1 more effectively restored erectile function than infection with AdAM alone or AdAng-1 alone. This combination therapy restored erectile function to a level similar to that observed in the age-matched Wistar rats. Expression of SMA and VE-cadherin increased more significantly in the AdAM plus AdAng-1-treated group than in the AdAM- or AdAng-1-treated group. Although AdVEGF-A infection restored erectile function significantly, it also caused enlargement of the trabeculae of the cavernous body, aberrant angiogenesis, and overproduction of type I collagen. These results suggested that combination therapy with AM and Ang-1 potently restored erectile function and normal morphology of the cavernous body compared with VEGF-A administration. This combination therapy will be useful to treat ED patients with a severely damaged cavernous body.

  7. Inhibition of SIRT1 combined with gemcitabine therapy for pancreatic carcinoma

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    Gong DJ

    2013-07-01

    Full Text Available Dao-Jun Gong,1 Jia-Min Zhang,1 Min Yu,1 Bo Zhuang,1 Qing-Qu Guo21Department of Hepatobiliary-Pancreatic Surgery, Jinhua Hospital of Zhejiang University, Jinhua, People's Republic of China; 2Department of Surgery, Second Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou, People's Republic of ChinaBackground: Pancreatic carcinoma possesses one of the highest lethality rates, highest drug-resistance, and highest incidence rates. The objective of this research was to enhance the efficacy and drug-resistance for pancreatic carcinoma by using inhibition of SIRT1 combined with gemcitabine therapy methods.Methods: Three pancreatic carcinoma cells (PANC-1 cells, BxPC-3 cells, and SW1990 cells received treatment with physiological saline, inhibition of SIRT1, gemcitabine, and combination therapy with inhibition of SIRT1 and gemcitabine in vitro; then BxPC-3 pancreatic cancer xenogeneic mice also received treatment with physiological saline, inhibition of SIRT1, gemcitabine, and combination therapy with inhibition of SIRT1 and gemcitabine in vivo.Results: The cleaved poly ADP ribose polymerase (PARP-1 effect of drug in pancreatic carcinoma cells was significantly different (P < 0.05 and the efficacy in descending order was the combination therapy with inhibition of SIRT1 and gemcitabine, inhibition of SIRT1, and gemcitabine. The BxPC-3 pancreatic cancer xenogeneic mice model received treatment with physiological saline, inhibition of SIRT1, gemcitabine, and combination therapy with inhibition of SIRT1 and gemcitabine in vivo and the results showed that the tumor volumes decreased and the survival rate within 45 days increased according to the order of the given drugs and the difference was significant (P < 0.05.Conclusion: Combination therapy with inhibition of SIRT1 and gemcitabine could improve efficacy and survival time in a BxPC-3 pancreatic cancer xenogeneic mice model, compared with single inhibition of SIRT1, or single

  8. Molecular analysis of hepatitis B virus (HBV in an HIV co-infected patient with reactivation of occult HBV infection following discontinuation of lamivudine-including antiretroviral therapy

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    Costantini Andrea

    2011-11-01

    Full Text Available Abstract Background Occult hepatitis B virus (HBV infection (OBI is characterized by HBV DNA persistence even though the pattern of serological markers indicates an otherwise resolved HBV infection. Although OBI is usually clinically silent, immunocompromised patients may experience reactivation of the liver disease. Case presentation We report the case of an individual with human immunodeficiency virus (HIV infection and anti-HBV core antibody positivity, who experienced severe HBV reactivation after discontinuation of lamivudine-including antiretroviral therapy (ART. HBV sequencing analysis showed a hepatitis B surface antigen escape mutant whose presence in an earlier sample excluded reinfection. Molecular sequencing showed some differences between two isolates collected at a 9-year interval, indicating HBV evolution. Resumption of ART containing an emtricitabine/tenofovir combination allowed control of plasma HBV DNA, which fell to undetectable levels. Conclusion This case stresses the ability of HBV to evolve continuously, even during occult infection, and the effectiveness of ART in controlling OBI reactivation in HIV-infected individuals.

  9. Radio-iodine therapy and Helicobacter pylori infection

    International Nuclear Information System (INIS)

    Gholamrezanezhad, A.; Mirpour, S.; Saghari, M.; Abdollahzadeh, J.; Pourmoslemi, A.; Yarmand, S.

    2008-01-01

    Helicobacter pylori is the most important cause of gastritis and related morbidities. Following consumption, radioactive iodine accumulates considerably in the stomach. On the basis of this observation, we decided to determine whether the high radiation induced by radio-iodine in the stomach is effective in the eradication of this infection. All consecutive patients with differentiated thyroid carcinoma, who were referred for radio-iodine therapy [dose 117.1±24.4 mCi (4.3±0.9 GBq), range 100-200 mCi (3.7-7.4 GBq)], were enrolled. To detect H. pylori infection, the urease breath test (UBT) was performed 1-2 h before radio-iodine consumption and the test was repeated 2 months later. Of 88 patients, 71 had pre-treatment positive UBT. Of these, 23 patients had negative post-treatment result, which means a significant reduction (26.1%, 95% confidence interval (CI) 16.8-35.5%) in the number of positive UBT results in our treated population (32.4% of UBT-positive cases became UBT-negative). Considering the high prevalence of reinfection in developing countries, the therapeutic benefit would have been more considerable if the second UBT had been done with a lag time of less than 2 months. Although radio-iodine therapy is not a logical method for the treatment of patients suffering from H. pylori, our finding provides indirect evidence about the radiosensitivity of bacteria, the future clinical applications of which need to be further evaluated. Also this finding can be useful for the food industry, where radiation is used widely to sterilize food. Regarding the possibility of H. pylori suppression, we recommend not using UBT for screening for the infection for at least within 2 months following radio-iodine therapy. (author)

  10. Effectiveness and Safety of Immunomodulators With Anti-Tumor Necrosis Factor Therapy in Crohn's Disease.

    Science.gov (United States)

    Osterman, Mark T; Haynes, Kevin; Delzell, Elizabeth; Zhang, Jie; Bewtra, Meenakshi; Brensinger, Colleen M; Chen, Lang; Xie, Fenglong; Curtis, Jeffrey R; Lewis, James D

    2015-07-01

    The benefit of continuing immunomodulators when "stepping up" to anti-tumor necrosis factor (anti-TNF) therapy for Crohn's disease (CD) is uncertain. This study assessed the effectiveness and safety of immunomodulators with anti-TNF therapy in CD. We conducted a retrospective cohort study of new users of anti-TNF therapy for CD in Medicare. Users of anti-TNF combination therapy with immunomodulators were matched to up to 3 users of anti-TNF monotherapy via propensity score and compared by using 3 metrics of effectiveness-surgery, hospitalization, and discontinuation of anti-TNF therapy or surgery-and 2 metrics of safety-serious infection and non-Candida opportunistic infection. Cox regression was used for all analyses. Among new users of infliximab, we matched 381 users of combination therapy to 912 users of monotherapy; among new users of adalimumab, we matched 196 users of combination therapy to 505 users of monotherapy. Combination therapy occurred predominantly as "step up" after thiopurine therapy. The rates of surgery (hazard ratio [HR], 1.20; 95% confidence interval, 0.73-1.96), hospitalization (HR, 0.82; 0.57-1.19), discontinuation of anti-TNF therapy or surgery (HR, 1.09; 0.88-1.34), and serious infection (HR, 0.93; 0.88-1.34) did not differ between users of anti-TNF combination therapy and monotherapy. However, the risks of opportunistic infection (HR, 2.64; 1.21-5.73) and herpes zoster (HR, 3.16; 1.25-7.97) were increased with combination therapy. We found that continuation of immunomodulators after "stepping up" to anti-TNF therapy did not improve outcomes but was associated with an increased risk of opportunistic infection. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  11. Impact of Combination Antimicrobial Therapy on Mortality Risk for Critically Ill Patients with Carbapenem-Resistant Bacteremia

    Science.gov (United States)

    Bauer, Seth R.; Neuner, Elizabeth A.; Lam, Simon W.

    2015-01-01

    There are limited treatment options for carbapenem-resistant Gram-negative infections. Currently, there are suggestions in the literature that combination therapy should be used, which frequently includes antibiotics to which the causative pathogen demonstrates in vitro resistance. This case-control study evaluated risk factors associated with all-cause mortality rates for critically ill patients with carbapenem-resistant Gram-negative bacteremia. Adult patients who were admitted to an intensive care unit with sepsis and a blood culture positive for Gram-negative bacteria resistant to a carbapenem were included. Patients with polymicrobial, recurrent, or breakthrough infections were excluded. Included patients were classified as survivors (controls) or nonsurvivors (cases) at 30 days after the positive blood culture. Of 302 patients screened, 168 patients were included, of whom 90 patients died (53.6% [cases]) and 78 survived (46.4% [controls]) at 30 days. More survivors received appropriate antibiotics (antibiotics with in vitro activity) than did nonsurvivors (93.6% versus 53.3%; P carbapenems) (87.2% versus 80%; P = 0.21). After adjustment for baseline factors with multivariable logistic regression, combination therapy was independently associated with decreased risk of death (odds ratio, 0.19 [95% confidence interval, 0.06 to 0.56]; P carbapenem-resistant Gram-negative bacteremia. However, that association is lost if in vitro activity is not considered. PMID:25845872

  12. Combined therapy of radiation and hyperthermia on a metastatic tumor of angiosarcoma

    International Nuclear Information System (INIS)

    Yasuda, Hiroshi; Kitayama, Yoshiaki

    1987-01-01

    A combined therapy of radiation and hyperthermia is said to be fairly effective when applied to certain malignant tumors. However, the utility of this therapy for the treatment of angiosarcoma has not been well discussed. Recently, we have had a chance to treat a patient with metastatic angiosarcoma of the neck by using this combined therapy. In this paper, the clinical course of this patient and the availability of this combined therapy for angiosarcoma is reported. The patient was a 77-year-old man, having a primary lesion on the head and a metastatic tumor over the left cheek and neck. This combined therapy was used for the treatment of the metastatic tumor which caused severe pain and uncontrollable bleeding. The results were considered good ; the tumor decreased in size, pain disappeared and no further bleeding or severe side effects were observed. Though the patient died of another metastatic lesion which could not be treated with this combined therapy because the area of its localization could not allow placement in our hyperthermal apparatus, it is concluded that the combined therapy of radiation and hyperthermia is useful selectively for the treatment for angiosarcoma. (author)

  13. Incidence of HIV-associated tuberculosis among individuals taking combination antiretroviral therapy: a systematic review and meta-analysis.

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    Tendesayi Kufa

    Full Text Available Knowledge of tuberculosis incidence and associated factors is required for the development and evaluation of strategies to reduce the burden of HIV-associated tuberculosis.Systematic literature review and meta-analysis of tuberculosis incidence rates among HIV-infected individuals taking combination antiretroviral therapy.From PubMed, EMBASE and Global Index Medicus databases, 42 papers describing 43 cohorts (32 from high/intermediate and 11 from low tuberculosis burden settings were included in the qualitative review and 33 in the quantitative review. Cohorts from high/intermediate burden settings were smaller in size, had lower median CD4 cell counts at study entry and fewer person-years of follow up. Tuberculosis incidence rates were higher in studies from Sub-Saharan Africa and from World Bank low/middle income countries. Tuberculosis incidence rates decreased with increasing CD4 count at study entry and duration on combination antiretroviral therapy. Summary estimates of tuberculosis incidence among individuals on combination antiretroviral therapy were higher for cohorts from high/intermediate burden settings compared to those from the low tuberculosis burden settings (4.17 per 100 person-years [95% Confidence Interval (CI 3.39-5.14 per 100 person-years] vs. 0.4 per 100 person-years [95% CI 0.23-0.69 per 100 person-years] with significant heterogeneity observed between the studies.Tuberculosis incidence rates were high among individuals on combination antiretroviral therapy in high/intermediate burden settings. Interventions to prevent tuberculosis in this population should address geographical, socioeconomic and individual factors such as low CD4 counts and prior history of tuberculosis.

  14. Combination stem cell therapy for heart failure

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    Ichim Thomas E

    2010-04-01

    Full Text Available Abstract Patients with congestive heart failure (CHF that are not eligible for transplantation have limited therapeutic options. Stem cell therapy such as autologous bone marrow, mobilized peripheral blood, or purified cells thereof has been used clinically since 2001. To date over 1000 patients have received cellular therapy as part of randomized trials, with the general consensus being that a moderate but statistically significant benefit occurs. Therefore, one of the important next steps in the field is optimization. In this paper we discuss three ways to approach this issue: a increasing stem cell migration to the heart; b augmenting stem cell activity; and c combining existing stem cell therapies to recapitulate a "therapeutic niche". We conclude by describing a case report of a heart failure patient treated with a combination stem cell protocol in an attempt to augment beneficial aspects of cord blood CD34 cells and mesenchymal-like stem cells.

  15. Combination therapy in patients with benign prostatic hyperplasia

    Directory of Open Access Journals (Sweden)

    Bojan Tršinar

    2006-11-01

    Full Text Available Background: The purpose of observational program of patients with lower urinary tract symptoms (LUTS because of benign prostatic hyperplasia (BPH (LUTS/BPH was to acquire additional pharmaco-epidemiological data on the safety and efficacy of combination therapy with finasteride and tamsulosin.Methods: Observational program of men with BPH was conducted in urological outpatient clinics in Slovenia from April 2004 until November 2005. In open-label, non-interventional program 1173 patients were observed, who had been treated because of LUTS/BPH with combination therapy with finasteride and tamsulosin, in the framework of common treatment. At baseline and after six months of treatment for each patient the International Prostatic Symptom Score (IPSS questionnaire and assessment of quality of life (QL were filled in. In addition, urinary flow rate and prostate volume were determined. Adverse effects of drugs were reported spontaneously. For statistical analysis the Student’s t-test was performed.Results: Combination therapy with finasteride and tamsulosin was well tolerated. 89 (7.6 % patients discontinued with medication because of lack of efficacy or because of adverse effects of drugs. Symptom score, assessment of quality of patients’ lives and volume of prostates were significantly lower (p < 0.0001, while urinary flow rate was significantly higher (p < 0.0001 after six months of treatment with finasteride and tamsulosin.Conclusions: Combination therapy of patients with LUTS/BPH with finasteride and tamsulosin is effective and safe.

  16. Transmitted drug resistant HIV-1 and association with virologic and CD4 cell count response to combination antiretroviral therapy in the EuroSIDA Study

    DEFF Research Database (Denmark)

    Bannister, Wendy P; Cozzi-Lepri, Alessandro; Clotet, Bonaventura

    2008-01-01

    OBJECTIVES: To investigate prevalence of transmitted drug-resistant human immunodeficiency virus (TDR) and factors associated with TDR and to compare virological and CD4 count response to combination antiretroviral therapy. METHODS: In this study, 525 mostly chronically infected EuroSIDA patients...

  17. Combination therapy of gastric carcinoma with radiation and chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Asakawa, Hiroshi; Otawa, Hirokazu; Yamada, Shogo; Matsumoto, Ko [Miyagi Prefectural Adult Disease Center, Natori (Japan)

    1982-08-01

    The concurrent combination therapy of radiation and chemotherapy was performed in a total of 134 cases of stomach cancer. Radiation response of tumor was remarkable in 35 (37%) of 95 cases, irradiated more than 5,000 rad. Yearly survival rates in 81 cases, in which the scheduled curative treatment was completed, were 63% in one, 31% in two, 21% in three, 17% in four and 13% in five years. These rates were intimately correlated to tumor size and cancer type. However, this combination therapy accompanied some fatal complications in a few percent. From the results, it was concluded that this combination therapy should be valuable to prolong the life of patients with gastric cancer, and that the curable indications for this treatment should be T1-T3: M0 cases with radio-responsive tumor.

  18. Childhood urinary tract infection caused by extended-spectrum β-lactamase-producing bacteria: Risk factors and empiric therapy.

    Science.gov (United States)

    Uyar Aksu, Nihal; Ekinci, Zelal; Dündar, Devrim; Baydemir, Canan

    2017-02-01

    This study investigated risk factors of childhood urinary tract infection (UTI) associated with extended-spectrum β-lactamase (ESBL)-producing bacteria (ESBL-positive UTI) and evaluated antimicrobial resistance as well as empiric treatment of childhood UTI. The records of children with positive urine culture between 1 January 2008 and 31 December 2012 were evaluated. Patients with positive urine culture for ESBL-producing bacteria were defined as the ESBL-positive group, whereas patients of the same gender and similar age with positive urine culture for non-ESBL-producing bacteria were defined as the ESBL-negative group. Each ESBL-positive patient was matched with two ESBL-negative patients. The ESBL-positive and negative groups consisted of 154 and 308 patients, respectively. Potential risk factors for ESBL-positive UTI were identified as presence of underlying disease, clean intermittent catheterization (CIC), hospitalization, use of any antibiotic and history of infection in the last 3 months (P infection in the last 3 months were identified as independent risk factors. In the present study, 324 of 462 patients had empiric therapy. Empiric therapy was inappropriate in 90.3% of the ESBL-positive group and in 4.5% of the ESBL-negative group. Resistance to nitrofurantoin was similar between groups (5.1% vs 1.2%, P = 0.072); resistance to amikacin was low in the ESBL-positive group (2.6%) and there was no resistance in the ESBL-negative group. Clean intermittent catheterization, hospitalization and history of infection in the last 3 months should be considered as risk factors for ESBL-positive UTI. The combination of ampicillin plus amikacin should be taken into consideration for empiric therapy in patients with acute pyelonephritis who have the risk factors for ESBL-positive UTI. Nitrofurantoin seems to be a logical choice for the empiric therapy of cystitis. © 2016 Japan Pediatric Society.

  19. Enhancing Photodynamyc Therapy Efficacy by Combination Therapy: Dated, Current and Oncoming Strategies

    International Nuclear Information System (INIS)

    Postiglione, Ilaria; Chiaviello, Angela; Palumbo, Giuseppe

    2011-01-01

    Combination therapy is a common practice in many medical disciplines. It is defined as the use of more than one drug to treat the same disease. Sometimes this expression describes the simultaneous use of therapeutic approaches that target different cellular/molecular pathways, increasing the chances of killing the diseased cell. This short review is concerned with therapeutic combinations in which PDT (Photodynamyc Therapy) is the core therapeutic partner. Besides the description of the principal methods used to assess the efficacy attained by combinations in respect to monotherapy, this review describes experimental results in which PDT was combined with conventional drugs in different experimental conditions. This inventory is far from exhaustive, as the number of photosensitizers used in combination with different drugs is very large. Reports cited in this work have been selected because considered representative. The combinations we have reviewed include the association of PDT with anti-oxidants, chemotherapeutics, drugs targeting topoisomerases I and II, antimetabolites and others. Some paragraphs are dedicated to PDT and immuno-modulation, others to associations of PDT with angiogenesis inhibitors, receptor inhibitors, radiotherapy and more. Finally, a look is dedicated to combinations involving the use of natural compounds and, as new entries, drugs that act as proteasome inhibitors

  20. Virological responses to lamivudine or emtricitabine when combined with tenofovir and a protease inhibitor in treatment-naïve HIV-1-infected patients in the Dutch AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort.

    Science.gov (United States)

    Rokx, C; Gras, L; van de Vijver, Damc; Verbon, A; Rijnders, Bja

    2016-09-01

    Lamivudine (3TC) and emtricitabine (FTC) are considered interchangeable in recommended tenofovir disoproxil-fumarate (TDF)-containing combination antiretroviral therapies (cARTs). This statement of equivalence has not been systematically studied. We compared the treatment responses to 3TC and FTC combined with TDF in boosted protease inhibitor (PI)-based cART for HIV-1-infected patients. An observational study in the AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort was carried out between 2002 and 2013. Virological failure rates, time to HIV RNA suppression treatment failure were analysed using multivariable logistic regression and Cox proportional hazard models. Sensitivity analyses included propensity score-adjusted models. A total of 1582 ART-naïve HIV-1-infected patients initiated 3TC or FTC with TDF and ritonavir-boosted darunavir (29.6%), atazanavir (41.5%), lopinavir (27.1%) or another PI (1.8%). Week 48 virological failure rates on 3TC and FTC were comparable (8.9% and 5.6%, respectively; P = 0.208). The multivariable adjusted odds ratio of virological failure when using 3TC instead of FTC with TDF in PI-based cART was 0.75 [95% confidence interval (CI) 0.32-1.79; P = 0.51]. Propensity score-adjusted models showed comparable results. The adjusted hazard ratio (HR) for treatment failure of 3TC compared with FTC was 1.15 (95% CI 0.58-2.27) within 240 weeks after cART initiation. The time to two consecutive HIV RNA measurements treatment failure after suppression treatment-naïve HIV-1-infected patients starting either 3TC/TDF or FTC/TDF and a ritonavir-boosted PI. © 2016 British HIV Association.

  1. Vacuum-assisted closure (VAC) therapy in the management of wound infection following renal transplantation.

    Science.gov (United States)

    Shrestha, B M; Nathan, V C; Delbridge, M C; Parker, K; Throssell, D; McKane, W S; Karim, M S; Raftery, A T

    2007-01-01

    Wound infection in the setting of immunosuppressed state such as renal transplantation (RT) causes significant morbidity from sepsis, prolongs hospital stay and is expensive. Vacuum-assisted closure (VAC) therapy is a new technique of management of wound based on the principle of application of controlled negative pressure. The aim of this study was to assess the efficacy of VAC therapy in the management of wound infection following RT. This is a prospective study of a cohort of 180 consecutive RTs performed over a period of 4 years, where the data were retrieved from a prospectively maintained computerised database and case-notes. 9 of 180 (5%) patients developed wound infection following RT which led to cavitations and dehiscence with copious discharge, and refused to heal with conventional treatment. All 9 cases were treated with VAC therapy. The VAC system was removed after a median of 9 (range 3-30) days when discharge from the wound ceased. Four patients were discharged home with portable VAC device and managed on an outpatient basis, where the system was removed after a median 5.5 (range 3-7) days. The median hospital stay after initiation of VAC therapy was significantly shorter (5, range 2-12 days) than on conventional treatment prior to VAC therapy (11, range, 5-20 days) (p=0.003). Complete healing was achieved in all cases. The use of VAC therapy is an effective and safe adjunct to conventional and established treatment modalities for the management of wound infection and dehiscence following RT. Key words: Renal transplantation, wound infection, vacuum-assisted closure therapy.

  2. Rapid Antiretroviral Therapy Initiation for Women in an HIV-1 Prevention Clinical Trial Experiencing Primary HIV-1 Infection during Pregnancy or Breastfeeding.

    Science.gov (United States)

    Morrison, Susan; John-Stewart, Grace; Egessa, John J; Mubezi, Sezi; Kusemererwa, Sylvia; Bii, Dennis K; Bulya, Nulu; Mugume, Francis; Campbell, James D; Wangisi, Jonathan; Bukusi, Elizabeth A; Celum, Connie; Baeten, Jared M

    2015-01-01

    During an HIV-1 prevention clinical trial in East Africa, we observed 16 cases of primary HIV-1 infection in women coincident with pregnancy or breastfeeding. Nine of eleven pregnant women initiated rapid combination antiretroviral therapy (ART), despite having CD4 counts exceeding national criteria for ART initiation; breastfeeding women initiated ART or replacement feeding. Rapid ART initiation during primary HIV-1 infection during pregnancy and breastfeeding is feasible in this setting.

  3. Rapid Antiretroviral Therapy Initiation for Women in an HIV-1 Prevention Clinical Trial Experiencing Primary HIV-1 Infection during Pregnancy or Breastfeeding.

    Directory of Open Access Journals (Sweden)

    Susan Morrison

    Full Text Available During an HIV-1 prevention clinical trial in East Africa, we observed 16 cases of primary HIV-1 infection in women coincident with pregnancy or breastfeeding. Nine of eleven pregnant women initiated rapid combination antiretroviral therapy (ART, despite having CD4 counts exceeding national criteria for ART initiation; breastfeeding women initiated ART or replacement feeding. Rapid ART initiation during primary HIV-1 infection during pregnancy and breastfeeding is feasible in this setting.

  4. Pretreatment CD4 cell slope and progression to AIDS or death in HIV-infected patients initiating antiretroviral therapy--the CASCADE collaboration: a collaboration of 23 cohort studies

    NARCIS (Netherlands)

    Wolbers, Marcel; Babiker, Abdel; Sabin, Caroline; Young, Jim; Dorrucci, Maria; Chêne, Geneviève; Mussini, Cristina; Porter, Kholoud; Bucher, Heiner C.; del Amo, Julia; Meyer, Laurence; Pillay, Deenan; Prins, Maria; Rosinska, Magda; Touloumi, Giota; Lodi, Sara; Coughlin, Kate; Walker, Sarah; Darbyshire, Janet; de Luca, Andrea; Fisher, Martin; Muga, Roberto; Kaldor, John; Kelleher, Tony; Ramacciotti, Tim; Gelgor, Linda; Cooper, David; Smith, Don; Gill, John; Jørgensen, Louise Bruun; Nielsen, Claus; Lutsar, Irja; Dabis, Francois; Thiebaut, Rodolphe; Masquelier, Bernard; Costagliola, Dominique; Guiguet, Marguerite; Vanhems, Philippe; Chaix, Marie-Laure; Ghosn, Jade; Boufassa, Faroudy; Hamouda, Osamah; Kucherer, Claudia; Pantazis, Nikos; Hatzakis, Angelos; Paraskevis, Dimitrios; Karafoulidoua, Anastasia; van der Helm, Jannie; Geskus, Ronald; Schuitemaker, Hanneke

    2010-01-01

    BACKGROUND: CD4 cell count is a strong predictor of the subsequent risk of AIDS or death in HIV-infected patients initiating combination antiretroviral therapy (cART). It is not known whether the rate of CD4 cell decline prior to therapy is related to prognosis and should, therefore, influence the

  5. Treatment Options for Carbapenem-Resistant and Extensively Drug-Resistant Acinetobacter baumannii Infections

    Science.gov (United States)

    Viehman, J. Alexander; Nguyen, Minh-Hong; Doi, Yohei

    2014-01-01

    Acinetobacter baumannii is a leading cause of healthcare-associated infections worldwide. Due to various intrinsic and acquired mechanisms of resistance, most β-lactam agents are not effective against many strains, and carbapenems have played an important role in therapy. Recent trends show many infections are caused by carbapenem-resistant, or even extensively drug-resistant (XDR) strains, for which effective therapy is not well established. Evidence to date suggests that colistin constitutes the backbone of therapy, but the unique pharmacokinetic properties of colistin have led many to suggest the use of combination antimicrobial therapy. However, the combination of agents and dosing regimens that delivers the best clinical efficacy while minimizing toxicity is yet to be defined. Carbapenems, sulbactam, rifampin and tigecycline have been the most studied in the context of combination therapy. Most data regarding therapy for invasive, resistant A. baumannii infections come from uncontrolled case series and retrospective analyses, though some clinical trials have been completed and others are underway. Early institution of appropriate antimicrobial therapy is shown to consistently improve survival of patients with carbapenem-resistant and XDR A. baumannii infection, but the choice of empiric therapy in these infections remains an open question. This review summarizes the most current knowledge regarding the epidemiology, mechanisms of resistance, and treatment considerations of carbapenem-resistant and XDR A. baumannii. PMID:25091170

  6. [Ganciclovir therapy for congenital cytomegalovirus infection in newborn infants: a meta analysis].

    Science.gov (United States)

    Hu, Jin-Tao; Chen, Ping-Yang; Xie, Zong-De; Dang, Xi-Qiang; Wang, Tao; He, Xiao-Ri; Li, Wen; Bo, Tao

    2010-01-01

    To evaluate the efficacy and safety of ganciclovir therapy for congenital cytomegalovirus (CMV) infection in newborn infants. The randomized controlled trials (RCTs) and quasi-RCTs on ganciclovir therapy for congenital CMV were reviewed in the following electronic databases: PubMed (January 1988 to January 2009), EMbase (January 1988 to January 2009), the Cochrane library (Issue 3, 2003 and Issue 1, 2009), the Chinese Journals Full-text Database (January 1994 to January 2009), the Chinese Biological Medical Disc (January 1994 to January 2009) and the Chinese Medical Current Contents (January 1994 to January 2009). Quality assessment, data extraction, and meta analysis were performed. Ten papers were included. Meta analysis showed that the ganciclovir therapy increased the improvement rate (91.4% vs 34.0%; pCMV infection indexes to become negative in more patients (87.6% vs 15.3%; pCMV infection indexes becoming negative, and decrease incidence of hearing disturbance, with few side effects, in newborn infants with CMV infection. However the supporting evidence is not strong due to few trials and more high-quality research is needed.

  7. Immunosuppressive therapy in non-infections uveitis and retinovasculitis

    OpenAIRE

    E. A. Drozdova

    2012-01-01

    Purpose: to evaluate the efficacy and safety of the immunosuppressive therapy for severe forms of non-infections uveitis and retinovasculitis.Methods: 107 patients (62 males and 45 females aged 9 to 54 years) who received low dose methotrexate — 7.5-20 mg once a week (n=79) cyclosporine A 3.5-5.0 mg/kg/d (n=21) with prednisone or other antimetabolites and local corticosteroid therapy for severe forms of inflammatory eye diseases.Results: the efficacy of methotrexate as monotherapy was 51.8% o...

  8. Activity of Colistin in Combination with Meropenem, Tigecycline, Fosfomycin, Fusidic Acid, Rifampin or Sulbactam against Extensively Drug-Resistant Acinetobacter baumannii in a Murine Thigh-Infection Model.

    Directory of Open Access Journals (Sweden)

    Bing Fan

    Full Text Available Few effective therapeutic options are available for treating severe infections caused by extensively drug-resistant Acinetobacter baumannii (XDR-AB. Using a murine thigh-infection model, we examined the in vivo efficacy of colistin in combination with meropenem, tigecycline, fosfomycin, fusidic acid, rifampin, or sulbactam against 12 XDR-AB strains. Colistin, tigecycline, rifampin, and sulbactam monotherapy significantly decreased bacterial counts in murine thigh infections compared with those observed in control mice receiving no treatment. Colistin was the most effective agent tested, displaying bactericidal activity against 91.7% of strains at 48 h post-treatment. With strains showing a relatively low minimum inhibitory concentration (MIC for meropenem (MIC ≤ 32 mg/L, combination therapy with colistin plus meropenem caused synergistic inhibition at both 24 h and 48 h post-treatment. However, when the meropenem MIC was ≥64 mg/L, meropenem did not significantly alter the efficacy of colistin. The addition of rifampin and fusidic acid significantly improved the efficacy of colistin, showing a synergistic effect in 100% and 58.3% of strains after 24 h of treatment, respectively, while the addition of tigecycline, fosfomycin, or sulbactam did not show obvious synergistic activity. No clear differences in activities were observed between colistin-rifampin and colistin-fusidic acid combination therapy with most strains. Overall, our in vivo study showed that administering colistin in combination with rifampin or fusidic acid is more efficacious in treating XDR-AB infections than other combinations. The colistin-meropenem combination may be another appropriate option if the MIC is ≤32 mg/L. Further clinical studies are urgently needed to confirm the relevance of these findings.

  9. Excess Mortality Associated With Colistin-Tigecycline Compared With Colistin-Carbapenem Combination Therapy for Extensively Drug-Resistant Acinetobacter baumannii Bacteremia: A Multicenter Prospective Observational Study.

    Science.gov (United States)

    Cheng, Aristine; Chuang, Yu-Chung; Sun, Hsin-Yun; Sheng, Wang-Huei; Yang, Chia-Jui; Liao, Chun-Hsing; Hsueh, Po-Ren; Yang, Jia-Ling; Shen, Ni-Jiin; Wang, Jann-Tay; Hung, Chien-Ching; Chen, Yee-Chun; Chang, Shan-Chwen

    2015-06-01

    Since few therapeutic options exist for extensively drug resistant Acinetobacter baumannii, an emerging threat in ICUs worldwide, and comparative prospective studies of colistin-based combination therapies are lacking, our objective was to compare the outcomes of patients with extensively drug-resistant A. baumannii bacteremia, treated with colistin-carbapenem and colistin-tigecycline combinations. Prospective, observational, multicenter study. Adults with extensively drug-resistant A. baumannii bacteremia were prospectively followed from 2010 to 2013 at three hospitals in Taiwan. Extensively drug-resistant A. baumannii was defined as A. baumannii (genospecies 2) nonsusceptible to all drug classes except for colistin and tigecycline, and standard combination therapy as use of parenteral colistin-carbapenem or colistin-tigecycline for at least 48 hours after onset of bacteremia. Primary outcome measure was 14-day mortality. Of the 176 episodes of extensively drug-resistant A. baumannii bacteremia evaluated, 55 patients with a median (interquartile range) age of 62 years (44-79 yr) and Sequential Organ Failure Assessment score of 9 (5-13) points received standard combination therapy: colistin-tigecycline in 29 patients and colistin-carbapenem in 26. Crude 14-day and in-hospital mortality rates for patients receiving colistin-tigecycline versus patients receiving colistin-carbapenem were 35% versus 15% (p=0.105) and 69% versus 50% (p=0.152), respectively. Breakthrough extensively drug-resistant A. baumannii bacteremia under steady state concentrations of combination therapy for colistin-tigecycline group was 18% and for colistin-carbapenem group was 0% (p=0.059). Eleven patients (20.0%) developed nephrotoxicity. After adjusting for age, sex, comorbidity, initial disease severity, loading colistin dose, polymicrobial infection, and primary infection site, excess 14-day mortality was associated with the use of colistin-tigecycline in the subgroup with tigecycline

  10. Combination ledipasvir-sofosbuvir for the treatment of chronic hepatitis C virus infection: a review and clinical perspective

    Directory of Open Access Journals (Sweden)

    Nkuize M

    2016-06-01

    Full Text Available Marcel Nkuize,1 Thomas Sersté,1,2 Michel Buset,1 Jean-Pierre Mulkay11Department of Gastroenterology and Hepatology, Saint-Pierre University Hospital, 2Department of Gastroenterology, Pancreatology and Hepatology, Hôpital Academique Erasme, Université Libre de Bruxelles, Brussels, Belgium Abstract: Chronic hepatitis C treatment has continued to evolve, and interferon-free, oral treatment with direct-acting antiviral agents is the current standard of care. Recently, a new treatment, which is a combination of two direct-acting antiviral agents, ledipasvir 90 mg (anti-NS5A and sofosbuvir 400 mg (anti-NS5B, has been approved in the US and the European Union for the treatment of chronic hepatitis C viral infection. In Phase III trials among chronic hepatitis C virus genotype 1 monoinfected (treatment-naïve, treatment-experienced, and with advanced liver disease or posttransplant patients and HIV–hepatitis C virus coinfected patients, the ledipasvir-sofosbuvir fixed-dose combination is associated with a higher rate of sustained virologic response at 12 weeks after therapy has ceased. According to preliminary data, the ledipasvir-sofosbuvir combination also may be effective against hepatitis C genotype 4 virus infection. The ledipasvir-sofosbuvir combination taken orally is generally well-tolerated. Moreover, the combination treatment may suppress the effect of predictive factors of chronic hepatitis C that have historically been known to be associated with treatment failure. Thus, the fixed-dose single-tablet combination of ledipasvir-sofosbuvir offers a new era for the effective treatment of a variety of patients suffering from chronic hepatitis C virus infection.Keywords: ledipasvir, liver disease, ethnicity, DAA, HIV

  11. Therapeutic Cancer Vaccines in Combination with Conventional Therapy

    DEFF Research Database (Denmark)

    Andersen, Mads Hald; Junker, N.; Ellebaek, E.

    2010-01-01

    The clinical efficacy of most therapeutic vaccines against cancer has not yet met its promise. Data are emerging that strongly support the notion that combining immunotherapy with conventional therapies, for example, radiation and chemotherapy may improve efficacy. In particular combination...

  12. Therapeutic cancer vaccines in combination with conventional therapy

    DEFF Research Database (Denmark)

    Andersen, Mads Hald; Junker, Niels; Ellebaek, Eva

    2010-01-01

    The clinical efficacy of most therapeutic vaccines against cancer has not yet met its promise. Data are emerging that strongly support the notion that combining immunotherapy with conventional therapies, for example, radiation and chemotherapy may improve efficacy. In particular combination...

  13. [Clostridium difficile infection: epidemiology, disease burden and therapy].

    Science.gov (United States)

    Gulácsi, László; Kertész, Adrienne; Kopcsóné Németh, Irén; Banai, János; Ludwig, Endre; Prinz, Gyula; Reményi, Péter; Strbák, Bálint; Zsoldiné Urbán, Edit; Baji, Petra; Péntek, Márta; Brodszky, Valentin

    2013-07-28

    C. difficile causes 25 percent of the antibiotic associated infectious nosocomial diarrhoeas. C. difficile infection is a high-priority problem of public health in each country. The available literature of C. difficile infection's epidemiology and disease burden is limited. Review of the epidemiology, including seasonality and the risk of recurrences, of the disease burden and of the therapy of C. difficile infection. Review of the international and Hungarian literature in MEDLINE database using PubMed up to and including 20th of March, 2012. The incidence of nosocomial C. difficile associated diarrhoea is 4.1/10 000 patient day. The seasonality of C. difficile infection is unproved. 20 percent of the patients have recurrence after metronidazole or vancomycin treatment, and each recurrence increases the chance of a further one. The cost of C. difficile infection is between 130 and 500 thousand HUF (430 € and 1665 €) in Hungary. The importance of C. difficile infection in public health and the associated disease burden are significant. The available data in Hungary are limited, further studies in epidemiology and health economics are required.

  14. Antibiotic therapy for preventing infections in people with acute stroke.

    Science.gov (United States)

    Vermeij, Jan-Dirk; Westendorp, Willeke F; Dippel, Diederik Wj; van de Beek, Diederik; Nederkoorn, Paul J

    2018-01-22

    Stroke is the main cause of disability in high-income countries and ranks second as a cause of death worldwide. Infections occur frequently after stroke and may adversely affect outcome. Preventive antibiotic therapy in the acute phase of stroke may reduce the incidence of infections and improve outcome. In the previous version of this Cochrane Review, published in 2012, we found that antibiotics did reduce the risk of infection but did not reduce the number of dependent or deceased patients. However, included studies were small and heterogeneous. In 2015, two large clinical trials were published, warranting an update of this Review. To assess the effectiveness and safety of preventive antibiotic therapy in people with ischaemic or haemorrhagic stroke. We wished to determine whether preventive antibiotic therapy in people with acute stroke:• reduces the risk of a poor functional outcome (dependency and/or death) at follow-up;• reduces the occurrence of infections in the acute phase of stroke;• reduces the occurrence of elevated body temperature (temperature ≥ 38° C) in the acute phase of stroke;• reduces length of hospital stay; or• leads to an increased rate of serious adverse events, such as anaphylactic shock, skin rash, or colonisation with antibiotic-resistant micro-organisms. We searched the Cochrane Stroke Group Trials Register (25 June 2017); the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 5; 25 June 2017) in the Cochrane Library; MEDLINE Ovid (1950 to 11 May 2017), and Embase Ovid (1980 to 11 May 2017). In an effort to identify further published, unpublished, and ongoing trials, we searched trials and research registers, scanned reference lists, and contacted trial authors, colleagues, and researchers in the field. Randomised controlled trials (RCTs) of preventive antibiotic therapy versus control (placebo or open control) in people with acute ischaemic or haemorrhagic stroke. Two review authors independently selected

  15. [Combination drug therapy in patients with BPH].

    Science.gov (United States)

    Kuzmenko, A V; Kuzmenko, V V; Gyaurgiev, T A

    2018-03-01

    Introuction. One of the risk factors for LUTS is an infravesical obstruction, which is most often caused by benign prostatic hyperplasia (BPH). BPH symptoms are formed due to three components: static (mechanical), dynamic, and impaired functional capacity of the bladder. Medical treatment with 1-blockers decreases the outflow obstruction. 5-alpha reductase inhibitors are used to inhibit the static component of BPH. To investigate the effectiveness of various modifications of medical therapy of BPH using -blockers and 5-reductase inhibitors and combinations thereof. The study comprised 90 BPH patients who were divided into three groups, with each group containing 30 people. Patients of group I, II and III received monotherapy with -blockers, a combination of 5-reductase and -blockers, and fixed-dose combination drug Duodart, respectively. Evaluation of the treatment effectiveness included filling out voiding diaries, completing the I-PSS and QL questionnaires, uroflowmetry, transrectal ultrasonography of the prostate and estimation of the incidence of adverse effects. Also, compliance with the treatment was evaluated, and the number of patients who had episodes of acute urinary retention and required surgical treatment during the 12 month treatment course was registered. Compared to monotherapy, combination therapy with -blockers and 5-reductase inhibitors more effectively reduces the LUTS, increases Qmax and prevents the disease progression, which manifests in a lower incidence of AUR and fewer surgical interventions in groups II and III. However, the combination therapy can be associated with some side effects. Patients who received fixed-dose combination drug Duodart had a greater compliance rate than patients on the combination of drugs, which, in our opinion, is associated with fewer cases of AUR and surgical interventions. The use of Duodart in patients with BPH effectively alleviates LUTS and reduces the risk of the disease progression, which manifests itself

  16. Interleukin-2 therapy in patients with HIV infection

    NARCIS (Netherlands)

    Abrams, D.; Lévy, Y.; Losso, M. H.; Babiker, A.; Collins, G.; Cooper, D. A.; Darbyshire, J.; Emery, S.; Fox, L.; Gordin, F.; Lane, H. C.; Lundgren, J. D.; Mitsuyasu, R.; Neaton, J. D.; Phillips, A.; Routy, J. P.; Tambussi, G.; Wentworth, D.; Aagaard, B.; Aragon, E.; Arnaiz, J.; Borup, L.; Clotet, B.; Dragsted, U.; Fau, A.; Gey, D.; Grarup, J.; Hengge, U.; Herrero, P.; Jansson, P.; Jensen, B.; Jensen, K.; Juncher, H.; Lopez, P.; Lundgren, J.; Matthews, C.; Mollerup, D.; Pearson, M.; Reilev, S.; Tillmann, K.; Varea, S.; Angus, B.; Cordwell, B.; Dodds, W.; Fleck, S.; Grijsen, M.; Lange, J.; Langebeek, N.; Reiss, P.; van der Horst, C.

    2009-01-01

    BACKGROUND: Used in combination with antiretroviral therapy, subcutaneous recombinant interleukin-2 raises CD4+ cell counts more than does antiretroviral therapy alone. The clinical implication of these increases is not known. METHODS: We conducted two trials: the Subcutaneous Recombinant, Human

  17. Transient Serotonin Toxicity Evoked by Combination of Electroconvulsive Therapy and Fluoxetine

    Directory of Open Access Journals (Sweden)

    René Klysner

    2014-01-01

    Full Text Available The serotonin syndrome has been described only in rare instances for electroconvulsive therapy combined with an antidepressant medication. We describe a case of serotonin toxicity induced by electroconvulsive therapy in combination with fluoxetine.

  18. Predictors and correlates of adherence to combination antiretroviral therapy (ART) for chronic HIV infection: a meta-analysis

    OpenAIRE

    Langebeek, Nienke; Gisolf, Elizabeth H; Reiss, Peter; Vervoort, Sigrid C; Hafsteinsdóttir, Thóra B; Richter, Clemens; Sprangers, Mirjam AG; Nieuwkerk, Pythia T

    2014-01-01

    Background Adherence to combination antiretroviral therapy (ART) is a key predictor of the success of human immunodeficiency virus (HIV) treatment, and is potentially amenable to intervention. Insight into predictors or correlates of non-adherence to ART may help guide targets for the development of adherence-enhancing interventions. Our objective was to review evidence on predictors/correlates of adherence to ART, and to aggregate findings into quantitative estimates of their impact on adher...

  19. Principles of etiopathogenetic therapy for acute respiratory viral infections in frequently ill children

    Directory of Open Access Journals (Sweden)

    L. A. Kharitonova

    2015-01-01

    Full Text Available Objective: to investigate the impact of incorporation of cycloferon into a therapy regimen on the efficiency of treatment for acute respiratory viral infections (ARVI in frequently ill children. Subjects and methods. The results of treatment were analyzed in 117 children divided into three groups according to the therapy regimen. Thus, symptomatic and local antiviral therapies (interferon nasal ointment and viferon suppositories were prescribed to all the children; furthermore, Group 1 (control used antibiotic therapy; Group 2 (Comparison Group 1 took antibiotics and cycloferon (tablets, and Group 3 (Comparison Group 2 had Cycloferon. Results: At the beginning of treatment, there was a reduction in interferon-a and interferon-y values with preserved serum interferon levels, suggesting the diminished compensatory responses ensuring antiviral protection. Analysis of the immune status revealed that virtually half of the children exhibited activation of compensatory mechanisms (stimulation of CD4+ and CD8+ production and an increase in NST test activity, one third displayed a disturbance (decreases in CD4+, CDlfrf, IgA, and NST test activity. After treatment, interferonogenesis was recovered in the majority (86,7% of the patients taking Cycloferon, in 74,1% of those who had a treatment regimen containing cycloferon and antibiotics, and only in 47,1 % of those who received antibiotics. Comparison of the immunological indicators during therapy with antibiotics alone or in combination with cycloferon demonstrated a more noticeable and balanced response to the latter: the normalized CD4+ and CD8+ values in the patients on antibiotic therapy was 8,9 and 5,8%, respectively, and 11,1 % in those who received antibiotics and cycloferon. Conclusion. Incorporation of cycloferon into ARVI treatment regimens for frequently ill patients has the positive effect on immunological indicators, which shows itself as recovery of initially diminished interferonogenesis

  20. Eradication of Salmonella Typhimurium infection in a murine model of typhoid fever with the combination of probiotic Lactobacillus fermentum ME-3 and ofloxacin

    Directory of Open Access Journals (Sweden)

    Karki Tõnis

    2008-08-01

    Full Text Available Abstract Background The aim of the study was to detect whether in experimental Salmonella enterica Typhimurium infection the probiotic Lactobacillus fermentum ME-3 in combination with fluoroquinolone therapy would eradicate S. Typhimurium, prevent the development of liver and spleen granulomas and improve the indices of oxidative stress in the ileum mucosa. The selected bacteriological, histological and biochemical methods were applied. Results Combined treatment with L. fermentum ME-3 and ofloxacin eradicated Salmonella Typhimurium from blood, ileum and liver, decreased the number of animals with liver and spleen granulomas and reduced the value of lipid peroxides in the ileum mucosa. Higher total counts of intestinal lactobacilli in all experimental groups were associated with the absence of liver granulomas. Conclusion The antimicrobial and antioxidative probiotic L. fermentum ME-3 combined with ofloxacin enhances the eradication of experimental S. Typhimurium infection. These observations on probiotic and antimicrobial co-action may serve as basis to develop new strategies for treatment of invasive bacterial infections of the gut.

  1. The use of combined radiation therapy and hormonal therapy in the management of lymph node-positive prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Whittington, Richard; Malkowicz, S Bruce; Machtay, Mitchell; Van Arsdalen, Keith; Barnes, Margaret M; Broderick, Gregory A; Wein, Alan J

    1997-10-01

    Purpose: To determine the rate of tumor response and patterns of relapse following combined hormonal-radiation therapy of adenocarcinoma of the prostate and to measure the survival in a group of men with tumor metastatic to pelvic lymph nodes. Methods and Materials: 66 patients with adenocarcinoma of the prostate with pathologically confirmed pelvic lymph node involvement were treated with combined radiation therapy and hormonal therapy. An additional five patients declined hormonal therapy. The patients treated with combined therapy represented a group with locally advanced disease including 44 patients (67%) with T3 or T4 tumors and 51 patients (80%) had N2 or N3 lymph node metastases. The pelvic lymph nodes were treated to a dose of 45 Gy and the prostate was boosted to a dose of 65 to 71 Gy. Hormonal therapy began up to 2 months before radiation and continued indefinitely. Patients were allowed to select their hormonal therapy and could choose DES (2 patients), orchiectomy (21 patients), LHRH agonist (7 patients) or combined androgen blockade (34 patients). Results: Median follow-up is 49 months (range 12 to 131 months) and 21 patients have been followed for longer than 5 years. There have been 15 recurrences the entire group including three local recurrences in the prostate, seven patients with distant metastases, four patients with biochemical recurrences without clinical evidence of disease, and one patient where the location was unknown. Two of the PSA recurrences occurred in patients who elected to discontinue hormones after less than 3 years of therapy. The overall survival at 5 and 8 years is 94 and 84%, the clinical disease free survival is 85 and 67%, and the biochemical disease-free survival is 78 and 47%. There was no increased toxicity of the combined modality regimen compared to the expected effects of radiation and hormonal therapy. Conclusion: Combined hormonal and radiation therapy represents an effective treatment option for patients with

  2. The use of combined radiation therapy and hormonal therapy in the management of lymph node-positive prostate cancer

    International Nuclear Information System (INIS)

    Whittington, Richard; Malkowicz, S. Bruce; Machtay, Mitchell; Van Arsdalen, Keith; Barnes, Margaret M.; Broderick, Gregory A.; Wein, Alan J.

    1997-01-01

    Purpose: To determine the rate of tumor response and patterns of relapse following combined hormonal-radiation therapy of adenocarcinoma of the prostate and to measure the survival in a group of men with tumor metastatic to pelvic lymph nodes. Methods and Materials: 66 patients with adenocarcinoma of the prostate with pathologically confirmed pelvic lymph node involvement were treated with combined radiation therapy and hormonal therapy. An additional five patients declined hormonal therapy. The patients treated with combined therapy represented a group with locally advanced disease including 44 patients (67%) with T3 or T4 tumors and 51 patients (80%) had N2 or N3 lymph node metastases. The pelvic lymph nodes were treated to a dose of 45 Gy and the prostate was boosted to a dose of 65 to 71 Gy. Hormonal therapy began up to 2 months before radiation and continued indefinitely. Patients were allowed to select their hormonal therapy and could choose DES (2 patients), orchiectomy (21 patients), LHRH agonist (7 patients) or combined androgen blockade (34 patients). Results: Median follow-up is 49 months (range 12 to 131 months) and 21 patients have been followed for longer than 5 years. There have been 15 recurrences the entire group including three local recurrences in the prostate, seven patients with distant metastases, four patients with biochemical recurrences without clinical evidence of disease, and one patient where the location was unknown. Two of the PSA recurrences occurred in patients who elected to discontinue hormones after less than 3 years of therapy. The overall survival at 5 and 8 years is 94 and 84%, the clinical disease free survival is 85 and 67%, and the biochemical disease-free survival is 78 and 47%. There was no increased toxicity of the combined modality regimen compared to the expected effects of radiation and hormonal therapy. Conclusion: Combined hormonal and radiation therapy represents an effective treatment option for patients with

  3. Polymorphism in interleukin-7 receptor α gene is associated with faster CD4 T-cell recovery after initiation of combination antiretroviral therapy

    DEFF Research Database (Denmark)

    Hartling, Hans J; Thørner, Lise W; Erikstrup, Christian

    2014-01-01

    OBJECTIVES: To investigate single-nucleotide polymorphisms (SNPs) in the gene encoding interleukin-7 receptor α (IL7RA) as predictors for CD4⁺ T-cell change after initiation of combination antiretroviral therapy (cART) in HIV-infected whites. DESIGN: SNPs in IL7RA were determined in the Danish HIV...

  4. Treatment of the Infection after Fat Injection

    Directory of Open Access Journals (Sweden)

    Seok-Kwun Kim

    2015-01-01

    Full Text Available For recent years, use of autologous fat injection has increased significantly in facial contouring surgery. Along with such increase in use, complications like atypical mycoplasma infection have been also on the increasing trend. The authors report two cases of Mycobacterium chelonae infection that occurred after autologous fat injection. Patients were treated as infection that resistant to common antibiotics and results were negative to routine culture and Gram staining. Acid-fast bacillus stain, polymerase chain reaction (PCR test and mycobacterial cultures were conducted for diagnosis under suspicion of atypical mycoplasma infection. Then, combination antibiotics therapy, surgical treatment, and steroid injection were performed for treatment. Both patients were diagnosed with Mycobacterium chelonae in PCR test. They were positive to mycobacterial cultures. Combination antibiotics therapy was repeated to improvement of symptom. However, they could not be free from side effects such as deformation in facial contour, scar and pigmentation even after full recovery. When chronic wound infections after autologous fat injection, we must suspect atypical or mycobacterial infection and conduct examinations for a early diagnosis and proper antibiotic therapy that is effective to the nontuberculous mycobacteria.

  5. Toxoplasmosis Complications and Novel Therapeutic Synergism Combination of Diclazuril plus Atovaquone

    Directory of Open Access Journals (Sweden)

    Helieh S Oz

    2014-09-01

    Full Text Available Toxoplasmosis is a major cause of foodborne disease, congenital complication and morbidity. There is an urgent need for safe and effective therapies to encounter congenital and persisting toxoplasmosis. The hypothesis was: Combination Diclazuril plus Atovaquone to exert a novel therapeutic synergy to prevent toxoplasmosis syndromes. Methods. Pregnant dams were treated with Diclazuril and Atovaquone monotherapy or combination therapy and infected intraperitoneally with Toxoplasma tachyzoites (600. Results. Infected dams developed severe toxoplasmosis associated syndrome with increases in the abdominal adiposity surrounding uteri, gansterointestinal and other internal organs and excessive weight gain. Numerous organisms along with infiltration of inflammatory cells were detected scattered into adipose tissues. Combination therapy (p< 0.01 and to a lesser extent Diclazuril (p< 0.05 protected dams from inflammatory fat and excess weight gains. This was consistent with pancreatitis development in infected dams (versus normal p< 0.05 with infiltration of inflammatory cells, degeneration and necrosis of pancreatic cells followed by the degeneration and loss of islets. Combination and monotherapy protected dams from these inflammatory and pathological aspects of pancreatitis. Infected dams exhibited severe colitis, and colonic tissues significantly shortened in length. Brush border epithelial cells were replaced with infiltration of lymphocytes, granulocytes, and microabscess formations into cryptic microstructures. Combination therapy synergistically preserved colonic structure and normalized pathological damages (p< 0.001 and to a lesser degree Diclazuril monotherapy protected dams from colitis (p< 0.05 and gastrointestinal toxoplasmosis. Other complications included severe splenitis (p<0.001 and hepatitis (p<0.001 which were normalized with combination therapy. Conclusions. Combination Diclazuril plus Atovaquone was safe and with a novel therapeutic

  6. Effectiveness of Thrombolytic Therapy in Acute Embolic Stroke due to Infective Endocarditis

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    Siva P. Sontineni

    2010-01-01

    Full Text Available Objective. To identify the role of thrombolytic therapy in acute embolic stroke due to infective endocarditis. Design. Case report. Setting. University hospital. Patient. A 70-year-old male presented with acute onset aphasia and hemiparesis due to infective endocarditis. His head computerized tomographic scan revealed left parietal sulcal effacement. He was given intravenous tissue plasminogen activator with significant resolution of the neurologic deficits without complications. Main Outcome Measures. Physical examination, National Institute of Health Stroke Scale, radiologic examination results. Conclusions. Thrombolytic therapy in selected cases of stroke due to infective endocarditis manifesting as major neurologic deficits can be considered as an option after careful consideration of risks and benefits. The basis for such favorable response rests in the presence of fibrin as a major constituent of the vegetation. The risk of precipitating hemorrhage with thrombolytic therapy especially with large infarcts and mycotic aneurysms should be weighed against the benefits of averting a major neurologic deficit.

  7. Interferon therapy of acute respiratory viral infections in children

    Directory of Open Access Journals (Sweden)

    A.E. Abaturov

    2017-04-01

    within the age limit and corresponded to the temperature response. Analyzing the dynamics of clinical symptoms of acute respiratory viral infection in both groups, it should be noted that there was a persistent tendency to lower body temperature in patients, both in the main and control groups. However, in the group of patients receiving Laferobionum®, the decrease in the temperature curve occurred faster, its normalization was noted already on the 4th day of therapy in 100 % of patients, whereas in the control group on the 4th day of the disease the body temperature remained subfebrile in 12 (28.6 %, on the 5th day — in 2 (4.8 % children. Complete blood count in children of the main and control groups at the beginning of the disease showed leukopenia of varying severity, relative lymphocytosis, and accelerated erythrocyte sedimentation rate (ESR. On the 5th day of therapy in patients of the main group, the number of leukocytes was normalized, the relative lymphocytosis persisted against the background of a decrease in ESR. While in the control group, the number of leukocytes in peripheral blood remained lower with an elevated level of ESR. During the whole period of observation, the presence and nature of possible complications of acute respiratory viral infection was assessed. The total duration of the observation period was 14 days. During the observation period, no complications were detected in any of the patients in the main or control groups. During the time of the clinical trial, no adverse reactions were recorded that could be associated with the administration of Laferobionum®. There were no cases of exacerbation of existing chronic diseases in the children of the main group, while 1 (2.4 % person from the control group had exacerbation of chronic tonsillitis. Evaluation of the effectiveness of therapy with the drug was carried out on the 5th day of treatment. Since one of the effectiveness criteria was the absence of clinical signs of the disease at the

  8. The role of combination medical therapy in the treatment of acromegaly.

    Science.gov (United States)

    Lim, Dawn Shao Ting; Fleseriu, Maria

    2017-02-01

    Uncontrolled acromegaly results in approximately 2-fold excess mortality. Pituitary surgery is first-line therapy, and medical treatment is indicated for persistent disease. While cabergoline and pegvisomant are used in select patients, somatostatin receptor ligands (SRLs) remain the cornerstone of medical treatment. Management of patients poorly responsive to SRLs is therefore, challenging. The purpose of this review is to highlight the options for combination medical therapy in the treatment of acromegaly, with an emphasis on efficacy and safety. All original articles/abstracts detailing combination medical therapy in acromegaly were identified from a PubMed search. Studies reviewed included retrospective and open-label prospective studies. While the combination of SRL and cabergoline was generally well tolerated, a lower baseline insulin-like growth factor-1 (IGF-1) level was the best predictor of efficacy; this combination may be most effective in patients with mildly elevated IGF-1. SRL-pegvisomant combination normalized IGF-1 in the majority of patients; continued efficacy despite individual drug dosing reduction was also reported. The risk of significant liver enzyme elevation was, however, higher than that reported with SRL monotherapy; close monitoring is recommended. Data on pegvisomant-cabergoline combination is limited, but this may be an option in the setting of SRL intolerance. Reports on temozolomide used in combination with other medical therapies in patients with aggressive GH-secreting tumors are also summarized. While more prospective, randomized controlled trials on long-term efficacy and safety are needed, combination medical therapy remains a treatment strategy that should be considered for acromegaly patients poorly responsive to SRLs.

  9. Current concepts in combination therapy for the treatment of hypertension: combined calcium channel blockers and RAAS inhibitors

    Directory of Open Access Journals (Sweden)

    Alberto F Rubio-Guerra

    2009-11-01

    Full Text Available Alberto F Rubio-Guerra1, David Castro-Serna2, Cesar I Elizalde Barrera2, Luz M Ramos-Brizuela21Metabolic and Research Clinic, 2Internal Medicine Department, Hospital General de Ticomán SS DF, MéxicoAbstract: Recent guidelines for the management of hypertension recommend target blood pressures <140/90 mmHg in hypertensive patients, or <130/80 mmHg in subjects with diabetes, chronic kidney disease, or coronary artery disease. Despite the availability and efficacy of antihypertensive drugs, most hypertensive patients do not reach the recommended treatment targets with monotherapy, making combination therapy necessary to achieve the therapeutic goal. Combination therapy with 2 or more agents is the most effective method for achieving strict blood pressure goals. Fixed-dose combination simplifies treatment, reduces costs, and improves adherence. There are many drug choices for combination therapy, but few data are available about the efficacy and safety of some specific combinations. Combination therapy of calcium antagonists and inhibitors of the renin-angiotensin-aldosterone system (RAAS are efficacious and safe, and have been considered rational by both the JNC 7 and the 2007 European Society of Hypertension – European Society of Cardiology guidelines for the management of arterial hypertension. The aim of this review is to discuss some relevant issues about the use of combinations with calcium channel blockers and RAAS inhibitors in the treatment of hypertension.Keywords: hypertension, calcium channel blockers, renin-angiotensin-aldosterone system inhibitors, fixed-dose combination, adherence

  10. Side effects of antiviral therapy in hepatitis C virus infection-sarcoidosis - case report.

    Science.gov (United States)

    Teodor, D; Teodor, Andra; Grigore, Lucia; Jugănariu, Gabriela; Dorobăţ, Carmen Mihaela; Miftode, Egidia; Azoicăi, Doina

    2012-01-01

    Standard therapy in chronic hepatitis C virus infection is still a combination of peginterferon alfa2a/2b and ribavirin for 48 weeks. As of side effects, there are organic side effects, such as hematologic disorders, and functional side effects, reflected in the quality of life of hepatitis C patients. Up to 30% of the patients develop specific side effects such as headache, fever, fatigue. Sarcoidosis, known as a granulomatous disease of uncertain cause, is an uncommon finding in this category of patients. This cause-effect relation is accounted for by the convergent action of peginterferon and ribavirin of stimulating type 1 T helper cells and reducing type 2 helper T cells activation. We present the case of male patient known with chronic hepatitis C who developed pulmonary sarcoidosis following antiviral therapy. The first manifestation of the disease was unexplained fever accompanied by pulmonary tract disease. The diagnosis was established by immunophenotyping in bronchial aspirate

  11. Response to combination antiretroviral therapy: variation by age

    DEFF Research Database (Denmark)

    Lundgren, Jens

    2008-01-01

    -naive individuals starting combination antiretroviral therapy from 1998 to 2006. OUTCOME MEASURES: Time from combination antiretroviral therapy initiation to HIV RNA less than 50 copies/ml (virological response), CD4 increase of more than 100 cells/microl (immunological response) and new AIDS/death were analysed...... response. The probability of virological response was lower in those aged 6-12 (adjusted hazard ratio: 0.87) and 13-17 (0.78) years, but was higher in those aged 50-54 (1.24), 55-59 (1.24) and at least 60 (1.18) years. The probability of immunological response was higher in children and younger adults...... and reduced in those 60 years or older. Those aged 55-59 and 60 years or older had poorer clinical outcomes after adjusting for the latest CD4 cell count. CONCLUSION: Better virological responses but poorer immunological responses in older individuals, together with low precombination antiretroviral therapy...

  12. Combinations of Radiation Therapy and Immunotherapy for Melanoma: A Review of Clinical Outcomes

    International Nuclear Information System (INIS)

    Barker, Christopher A.; Postow, Michael A.

    2014-01-01

    Radiation therapy has long played a role in the management of melanoma. Recent advances have also demonstrated the efficacy of immunotherapy in the treatment of melanoma. Preclinical data suggest a biologic interaction between radiation therapy and immunotherapy. Several clinical studies corroborate these findings. This review will summarize the outcomes of studies reporting on patients with melanoma treated with a combination of radiation therapy and immunotherapy. Vaccine therapies often use irradiated melanoma cells, and may be enhanced by radiation therapy. The cytokines interferon-α and interleukin-2 have been combined with radiation therapy in several small studies, with some evidence suggesting increased toxicity and/or efficacy. Ipilimumab, a monoclonal antibody which blocks cytotoxic T-lymphocyte antigen-4, has been combined with radiation therapy in several notable case studies and series. Finally, pilot studies of adoptive cell transfer have suggested that radiation therapy may improve the efficacy of treatment. The review will demonstrate that the combination of radiation therapy and immunotherapy has been reported in several notable case studies, series and clinical trials. These clinical results suggest interaction and the need for further study

  13. Combinations of Radiation Therapy and Immunotherapy for Melanoma: A Review of Clinical Outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Barker, Christopher A., E-mail: barkerc@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Postow, Michael A. [Department of Medicine, Melanoma and Sarcoma Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2014-04-01

    Radiation therapy has long played a role in the management of melanoma. Recent advances have also demonstrated the efficacy of immunotherapy in the treatment of melanoma. Preclinical data suggest a biologic interaction between radiation therapy and immunotherapy. Several clinical studies corroborate these findings. This review will summarize the outcomes of studies reporting on patients with melanoma treated with a combination of radiation therapy and immunotherapy. Vaccine therapies often use irradiated melanoma cells, and may be enhanced by radiation therapy. The cytokines interferon-α and interleukin-2 have been combined with radiation therapy in several small studies, with some evidence suggesting increased toxicity and/or efficacy. Ipilimumab, a monoclonal antibody which blocks cytotoxic T-lymphocyte antigen-4, has been combined with radiation therapy in several notable case studies and series. Finally, pilot studies of adoptive cell transfer have suggested that radiation therapy may improve the efficacy of treatment. The review will demonstrate that the combination of radiation therapy and immunotherapy has been reported in several notable case studies, series and clinical trials. These clinical results suggest interaction and the need for further study.

  14. An assessment of antibiotic therapy of urinary tract infection in elderly, hospitalised patients.

    Science.gov (United States)

    McCaig, D J; Stewart, D; Harvey, Y; Downie, G; Scott, C J

    1995-11-01

    The aim of the study was to compare the antibiotic treatment actually received by elderly, hospitalised patients with urinary tract infection (UTI) with 'optimal' therapy (as gauged by compliance with antibiotic policy, infecting organism, sensitivity data, patient renal function and cost). UTI was more common in females and in catheterised patients and E.Coli was the commonest pathogen. Trimethoprim and co-amoxiclav were the drugs used most frequently for either empirical or sensitivity data-based treatment. In 96% of infections a drug with appropriate action was administered. Often, however, treatment could have been optimised by substituting a cheaper suitable antibiotic, by standardising duration of therapy and ensuring that doses were adjusted for renal impairment. Savings from the use of 'optimal' therapy were estimated at 17%. There is clearly considerable scope for positive input from the clinical pharmacist in this area.

  15. Antibiotic Desensitization Therapy in Secondary Syphilis and Listeria Infection: Case Reports and Review of Desensitization Therapy

    Science.gov (United States)

    Magpantay, Gil; Madar, Cristian S; Hsue, Gunther; Belnap, Conrad

    2011-01-01

    Two adult cases, one of secondary syphilis and one of Listeria monocytogenes bacteremia, in which antibiotic desensitization therapy was utilized to assist treatment of active infection in the face of severe penicillin allergy. Clinical considerations are discussed that led to the decision to employ a formal desensitization procedure. Antibiotic desensitization protocols can facilitate optimal and safe antibiotic therapy in the appropriate clinical setting. PMID:22187514

  16. Synergistic combination therapy of antitumor agents, membrane modification agents and irradiation

    International Nuclear Information System (INIS)

    Watarai, Jiro; Itagaki, Takatomo; Akutsu, Thoru; Yamaguchi, Kouichi; Kato, Isao

    1983-01-01

    Larygeal cancer were treated with synergistic combination therapy of Futraful in suppository, vitamin A, cepharanthin and irradiation from April 1981 to June 1982. This combination therapy resulted in high percentage of the tumor regression in the case of the invading laryngeal cancer and negligible complication. (author)

  17. Central Nervous System Strongyloidiasis and Cryptococcosis in an HIV-Infected Patient Starting Antiretroviral Therapy

    Directory of Open Access Journals (Sweden)

    Mónica Rodríguez

    2012-01-01

    Full Text Available We report a case of Strongyloides stercoralis hyperinfection syndrome with central nervous system involvement, in a patient with late human immunodeficiency virus (HIV infection starting antiretroviral therapy, in whom Strongyloides stercoralis larvae and Cryptococcus neoformans were isolated antemortem from cerebrospinal fluid. Our patient was not from an endemic region for the parasite, so strongyloidiasis was not originally suspected. For this reason, we conclude that Strongyloides stercoralis infection should be suspected in HIV-infected patients starting antiretroviral therapy in order to avoid potential fatal outcomes.

  18. [Vacuum-assisted closure therapy for the treatment of sternal wound infection after cardiac surgery].

    Science.gov (United States)

    Nishimura, K; Nakamura, Y; Harada, S; Saiki, M; Marumoto, A; Kanaoka, Y; Nishimura, M

    2009-11-01

    Sternal wound infection is still one of the critical and challenging complications after cardiac surgery. Vacuum-assisted closure (VAC) therapy is a unique and simple system that helps promote wound healing. We report 3 cases with the sternal wound infection after cardiac surgery, in which VAC therapy was applied between January, 2005 and April, 2007. Two of them had good response to VAC therapy and had their wound healed after 3 and 5 weeks, respectively. However, the remaining case, in which bilateral internal thoracic artery had been taken down for coronary artery bypass grafting (CABG) and osteomyelitis of the sternum was not well controlled, did not respond to VAC therapy. Our results suggested that VAC might facilitate wound healing of the patients with sternal wound infection only after abscess was drained and opened, while it might not be useful for the patents with osteomyelitis.

  19. Short Communication: Hyperthyroidism in Human Immunodeficiency Virus Patients on Combined Antiretroviral Therapy: Case Series and Literature Review.

    Science.gov (United States)

    Hsu, Emory; Phadke, Varun K; Nguyen, Minh Ly T

    2016-06-01

    We describe an HIV-infected patient initiated on combined antiretroviral therapy (cART) who subsequently developed immune restoration disease (IRD) hyperthyroidism-this case represents one of five such patients seen at our center within the past year. Similar to previous reports of hyperthyroidism due to IRD, all of our patients experienced a rapid early recovery in total CD4 count, but developed symptoms of hyperthyroidism on average 3 years (38 months) after beginning cART, which represents a longer time frame than previously reported. Awareness and recognition of this potential complication of cART, which may occur years after treatment initiation, will allow patients with immune restorative hyperthyroidism to receive timely therapy and avoid the long-term complications associated with undiagnosed thyroid disease.

  20. Radiotherapy in combination with vascular-targeted therapies

    International Nuclear Information System (INIS)

    Ciric, Eva; Sersa, Gregor

    2010-01-01

    Given the critical role of tumor vasculature in tumor development, considerable efforts have been spent on developing therapeutic strategies targeting the tumor vascular network. A variety of agents have been developed, with two general approaches being pursued. Antiangiogenic agents (AAs) aim to interfere with the process of angiogenesis, preventing new tumor blood vessel formation. Vascular-disrupting agents (VDAs) target existing tumor vessels causing tumor ischemia and necrosis. Despite their great therapeutic potential, it has become clear that their greatest clinical utility may lie in combination with conventional anticancer therapies. Radiotherapy is a widely used treatment modality for cancer with its distinct therapeutic challenges. Thus, combining the two approaches seems reasonable. Strong biological rationale exist for combining vascular-targeted therapies with radiation. AAs and VDAs were shown to alter the tumor microenvironment in such a way as to enhance responses to radiation. The results of preclinical and early clinical studies have confirmed the therapeutic potential of this new treatment strategy in the clinical setting. However, concerns about increased normal tissue toxicity, have been raised

  1. Microwave therapy for cutaneous human papilloma virus infection.

    Science.gov (United States)

    Bristow, Ivan; Lim, Wen Chean; Lee, Alvin; Holbrook, Daniel; Savelyeva, Natalia; Thomson, Peter; Webb, Christopher; Polak, Marta; Ardern-Jones, Michael R

    2017-10-01

    Human papilloma virus (HPV) infects keratinocytes of the skin and mucous membranes, and is associated with the induction of cutaneous warts and malignancy. Warts can induce significant morbidity and disability but most therapies, including cryotherapy, laser, and radiofrequency devices show low efficacy and induce discomfort through tissue destruction. Microwaves are readily capable of passing through highly keratinised skin to deliver energy and induce heating of the tissue in a highly controllable, uniform manner. To determine the effects of microwave on cutaneous HPV infection. We undertook a pilot study of microwave therapy to the skin in 32 consecutive individuals with 52 recalcitrant long-lived viral cutaneous warts. Additionally, we undertook a molecular characterisation of the effects of microwaves on the skin. Tissue inflammation was minimal, but 75.9% of lesions cleared which compares favourably with previous studies showing a clearance rate of 23-33% for cryotherapy or salicylic acid. We show that microwaves specifically induce dendritic cell cross-presentation of HPV antigen to CD8+ T cells and suggest that IL-6 may be important for DC IRF1 and IRF4 modulation to enhance this process. Keratinocyte-skin dendritic cell cross-talk is integral to host defence against HPV infections, and this pilot study supports the concept of microwave induction of anti-HPV immunity which offers a promising approach for treatment of HPV-induced viral warts and potentially HPV-related cancers.

  2. Pancreatitis associated with potassium bromide/phenobarbital combination therapy in epileptic dogs.

    OpenAIRE

    Gaskill, C L; Cribb, A E

    2000-01-01

    In a retrospective study, at least 10% of dogs receiving potassium bromide/phenobarbital combination therapy, compared with 0.3% of dogs receiving phenobarbital monotherapy, had probable pancreatitis. Pancreatitis may be a more frequent and more serious adverse effect of potassium bromide/phenobarbital combination therapy than has been reported previously.

  3. Diagnosis and treatment of Helicobacter pylori infection

    DEFF Research Database (Denmark)

    Bytzer, Peter; Dahlerup, Jens Frederik; Eriksen, Jens Ravn

    2011-01-01

    with a rapid urease test. Proton pump inhibitor therapy should be stopped at least 1 week prior to Hp testing. All infected patients should be offered Hp eradication therapy. First-line treatment is 7-day triple therapy with a proton pump inhibitor and clarithromycine in combination with metronidazole...

  4. [Antimicrobial treatment in complicated intraabdominal infections--current situation].

    Science.gov (United States)

    Vyhnánek, F

    2009-04-01

    Compared to other infections, intraabdominal infections include wide spectrum of infections of various severity, have different ethiology, which is frequently polymicrobial, show different microbiological results, which are difficult to interpret. The role of surgical intervention is essential. Intraabdominal infections are common causes of morbidity and mortality. Their prognosis is significantly improved with early and exact diagnosis, appropriate surgical or radiological intervention and timely effective antimicrobial therapy. Practitioners may choose between older or more modern antibiotics, between monotherapy or combination therapy, however, they should also consider clinical condition of the patient, the antibiotic's spectrum of activity, the treatment timing and its duration, the dose and dosing scheme of the particular antimicrobials. Furthermore, antimicrobial therapy should be used with caution, with the aim to prevent development of antimicrobial resistence. Inappropriate choice of antimicrobials in initial empiric therapy results in relapsing infections, surgical intervention and prolongation of hospitalization, and even death rates reflect adequate and timely empiric therapy.

  5. Is there a decline in cognitive functions after combined electroconvulsive therapy and antipsychotic therapy in treatment-refractory schizophrenia?

    Science.gov (United States)

    Pawełczyk, Agnieszka; Kołodziej-Kowalska, Emilia; Pawełczyk, Tomasz; Rabe-Jabłońska, Jolanta

    2015-03-01

    An analysis of literature shows that there is still little evidence concerning the efficacy of electroconvulsive therapy (ECT) combined with antipsychotic therapy in a group of treatment-resistant schizophrenia patients. More precisely, its influence on cognitive functions is still equivocal. The aim of this study was to assess the influence of ECT combined with antipsychotic therapy on working memory, attention, and executive functions in a group of treatment-refractory schizophrenia patients. Twenty-seven patients completed the study: 14 men and 13 women, aged 21 to 55 years (mean age, 32.8 years), diagnosed with treatment-resistant schizophrenia. Each patient underwent a course of ECT sessions and was treated with antipsychotic medications. Before the ECT and within 3 days after the last ECT session, the participants were assessed with the following neuropsychological tests: Trail Making Test (TMT) and Wisconsin Cart Sorting Test (WCST). There were no significant differences in the TMT and WCST results after combined ECT and antipsychotic therapy in treatment-refractory schizophrenia patients. According to the results of the neuropsychological tests, there was no decline in attention, executive functions, or working memory. The current study shows no significant difference in attention, working memory, or executive functions after treatment with a combination of electroconvulsive and antipsychotic therapy. This suggests that combined electroconvulsive therapy may not have a negative influence on the neuropsychological functioning of patients with treatment resistant schizophrenia.

  6. HIV INFECTION, ANTIRETROVIRAL THERAPY AND CARDIOVASCULAR RISK

    Directory of Open Access Journals (Sweden)

    Katleen de Gaetano Donati

    2010-11-01

    Full Text Available In the last 15 years, highly active antiretroviral therapy (HAART has determined a dramatic reduction of both morbidity and mortality in human immunodeficiency virus (HIV-infected subjects, transforming this infection in a chronic and manageable disease. Patients surviving with HIV in the developed world, in larger number men,  are becoming aged. As it would be expected for a population of comparable age, many HIV-infected individuals report a family history of cardiovascular disease, a small proportion have already experienced a cardiovascular event and an increasing proportion has diabetes mellitus. Smoking rate is very high while an increasing proportion of HIV-infected individuals have dyslipidaemia. Studies suggest that these traditional risk factors could play an important  role in the development of cardiovascular disease in these patients as they do in the general population. Thus, whilst the predicted 10-year cardiovascular disease risk remains relatively low at present, it will likely increase in relation to the progressive aging of  this patient population. Thus, the long-term follow-up of HIV infected patients has to include co-morbidity management such as cardiovascular disease prevention and treatment. Two intriguing aspects related to the cardiovascular risk in patients with HIV infection are the matter of current investigation: 1 while these subjects share many cardiovascular risk factors with the general population, HIV infection itself increases cardiovascular risk; 2 some HAART regimens too influence atherosclerotic profile, partly due to lipid changes. Although the mechanisms involved in the development of cardiovascular complications in HIV-infected patients remain to be fully elucidated, treatment guidelines recommending interventions to prevent cardiovascular disease in these individuals are already available; however, their application is still limited.

  7. THE ROLE OF PHYTOMEDICATIONS IN COMPLEX THERAPY OF URINAL INFECTIONS IN CHILDREN

    Directory of Open Access Journals (Sweden)

    M.A. Mamaeva

    2008-01-01

    Full Text Available High prevalence of urinal infections (UI in children, high rate of relapse and increase of antibiotic resistance force specialists to search a new complex methods of anti relapse therapy. Analysis of 380 medical cards of children showed that phytotherapy is not always used correctly; in spite of it can be important part of anti relapse therapy. The activity of different schemes of treatment of UI with phytomedicament «canephron n» included in it was studied in 110 children (aged from 5 month to 15 years. Children treated with complex therapy with antibiotics and phytomedication had no relapse in 99% of cases in 6 months and in 91% in 1 year follow up.Key words: children, urinal infections, phytotherapy.

  8. Combined Antirelapse Therapy in Patients with Schizoaffective Disorder: A Prospective Cohort Study

    Directory of Open Access Journals (Sweden)

    Zhanna R. Gardanova

    2016-06-01

    Full Text Available Background: In most studies, patients with schizoaffective disorder (SAD are often combined into one group along with schizophrenia patients or less commonly with those suffering from affective disorders, which makes it difficult to obtain data about the peculiarities of SAD treatment. Articles dedicated to SAD treatment in the interictal period are rare. Methods and Results: The prospective cohort study was conducted from 2011 to 2015. The study involved 86 patients diagnosed with SAD according to ICD-10. Patients received neuroleptics (NLs as antirelapse therapy for 2 years (NL therapy; then mood stabilizers (MSs were added to the antirelapse treatment (NL+MS therapy. The results of this combined therapy with MSs were evaluated after 2 years of treatment. Our results suggest that the use of combination therapy that includes antipsychotics and MSs leads to maintenance of a higher quality remission. Remission becomes more prolonged and affective swings less pronounced, resulting in improved quality of life in SAD patients. Improving the quality of remission can be attributed to the following characteristics of the combined therapy: a the use of lower doses of neuroleptics; b a reduction in the frequency and severity of mood swings; and c an increase in patient compliance. Conclusion: The use of combined pharmacotherapy including antipsychotics and MSs produces a longer, high-quality remission. The inclusion of MSs in the scheme of treatment increases the patient adherence to a medication regimen. The use of MSs in combination therapy reduces affective fluctuations, thereby increasing the probability of maintaining remission with complete symptom relief.

  9. Travel and biologic therapy: travel-related infection risk, vaccine response and recommendations.

    Science.gov (United States)

    Hall, Victoria; Johnson, Douglas; Torresi, Joseph

    2018-01-01

    Biologic therapy has revolutionized the management of refractory chronic autoimmune and auto-inflammatory disease, as well as several malignancies, providing rapid symptomatic relief and/or disease remission. Patients receiving biologic therapies have an improved quality of life, facilitating travel to exotic destinations and potentially placing them at risk of a range of infections. For each biologic agent, we review associated travel-related infection risk and expected travel vaccine response and effectiveness. A PUBMED search [vaccination OR vaccine] AND/OR ['specific vaccine'] AND/OR [immunology OR immune response OR response] AND [biologic OR biological OR biologic agent] was performed. A review of the literature was performed in order to develop recommendations on vaccination for patients in receipt of biologic therapy travelling to high-risk travel destinations. There is a paucity of literature in this area, however, it is apparent that travel-related infection risk is increased in patients on biologic therapy and when illness occurs they are at a higher risk of complication and hospitalization. Patients in receipt of biologic agents are deemed as having a high level of immunosuppression-live vaccines, including the yellow fever vaccine, are contraindicated. Inactivated vaccines are considered safe; however, vaccine response can be attenuated by the patient's biologic therapy, thereby resulting in reduced vaccine effectiveness and protection. Best practice requires a collaborative approach between the patient's primary healthcare physician, relevant specialist and travel medicine expert, who should all be familiar with the immunosuppressive and immunomodulatory effects resulting from the biologic therapies. Timing of vaccines should be carefully planned, and if possible, vaccination provided well before established immunosuppression.

  10. Testosterone Replacement Therapy and Polycythemia in HIV-infected Patients

    Science.gov (United States)

    Vorkas, Charles Kyriakos; Vaamonde, Carlos M.; Glesby, Marshall J.

    2013-01-01

    We conducted a case-control study to assess testosterone use as a primary risk factor for polycythemia in 21 HIV-infected men. Any testosterone use within two months of first elevated hemoglobin was associated with polycythemia (matched odds ratio 6.55; 95% CI 1.83-23.4; P=0.004) and intramuscular administration demonstrated a stronger association than topical use. No adverse cardiovascular or thrombotic events were observed. HIV-infected patients taking testosterone should undergo routine hematologic monitoring with adjustment of therapy when appropriate. PMID:22008652

  11. Therapy-refractory Panton Valentine Leukocidin-positive community-acquired methicillin-sensitive Staphylococcus aureus sepsis with progressive metastatic soft tissue infection: a case report

    Directory of Open Access Journals (Sweden)

    Schefold Joerg C

    2007-12-01

    Full Text Available Abstract We report a case of fulminant multiple organ failure including the Acute Respiratory Distress Syndrome (ARDS, haemodynamic, and renal failure due to community-acquired methicillin-sensitive Panton Valentine Leukocidin (PVL positive spa-type 284 (ST121 Staphylococcus aureus septic shock. The patient's first clinical symptom was necrotizing pneumonia. Despite organism-sensitive triple antibiotic therapy with linezolid, imipenem and clindamycin from the first day of treatment, progressive abscess formation in multiple skeletal muscles was observed. As a result, repeated surgical interventions became necessary. Due to progressive soft tissue infection, the anti-microbial therapy was changed to a combination of clindamycin and daptomycin. Continued surgical and antimicrobial therapy finally led to a stabilisation of the patients' condition. The clinical course of our patient underlines the existence of a "PVL-syndrome" which is independent of in vitro Staphylococcus aureus susceptibility. The PVL-syndrome should not only be considered in patients with soft tissue or bone infection, but also in patients with pneumonia. Such a condition, which may easily be mistaken for uncomplicated pneumonia, should be treated early, aggressively and over a long period of time in order to avoid relapsing infection.

  12. Treating Hypothyroidism with Thyroxine/Triiodothyronine Combination Therapy in Denmark

    DEFF Research Database (Denmark)

    Michaelsson, Luba Freja; Medici, Bjarke Borregaard; la Cour, Jeppe Lerche

    2015-01-01

    BACKGROUND: Five to ten percent of patients with hypothyroidism describe persistent symptoms despite being biochemically well regulated on levothyroxine (L-T4). Thyroxine (T4)/triiodothyronine (T3) combination therapy [L-T4/liothyronine (L-T3) or desiccated thyroid] are still regarded as experime......BACKGROUND: Five to ten percent of patients with hypothyroidism describe persistent symptoms despite being biochemically well regulated on levothyroxine (L-T4). Thyroxine (T4)/triiodothyronine (T3) combination therapy [L-T4/liothyronine (L-T3) or desiccated thyroid] are still regarded...

  13. The effects of combining ionizing radiation and adenoviral p53 therapy in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Li Jianhua; Lax, Stuart A.; Kim, John; Klamut, Henry; Liu Feifei

    1999-01-01

    Purpose: Nasopharyngeal carcinoma (NPC) is a malignant disease of the head/neck region, with a 5-year survival level of approximately 65%. To explore gene therapy as a novel approach which might improve outcome, we have shown previously that introduction of human recombinant wild-type p53 mediated by the adenoviral vector (Ad5CMV-p53) was cytotoxic in two human nasopharyngeal carcinoma (NPC) cell lines (CNE-1 and CNE-2Z). The current work was designed to determine whether this strategy, combined with ionizing radiation (XRT), was more effective than either treatment alone. Methods and Materials: CNE-1, CNE-2Z, and a normal human nasopharyngeal fibroblast strain, KS1, were infected with 2- and 6-plaque-forming units (pfu)/cell of Ad5CMV-p53, respectively. These doses were iso-effective for β-galactosidase activity in the CNE-1 and CNE-2Z cells. XRT was administered 24 h post-infection, and Western blot analyses were conducted for p53, p21 WAF1/CIP1 , bax, and bcl-2 2 days after XRT. Cell survival was assessed using a clonogenic assay. Presence of DNA ladders reflecting apoptosis was detected using DNA agarose gel electrophoresis, and cell cycle was analyzed using flow cytometry. Results: The combination of Ad5CMV-p53 plus XRT (2, 4, and 6 Gy) resulted in an approximately 1-log greater level of cytotoxicity compared to that observed with XRT alone for both NPC cell lines. The two modalities appear to be interacting in a synergistic manner in cancer cells, but not in KS1 fibroblasts. XRT alone stimulated minimal p53 expression in control cells; Ad5CMV-p53 alone induced significant recombinant p53 expression, which was not further enhanced by the addition of XRT. Similar observations were made for p21 WAF1/CIP1 expression. No changes were observed for bax or bcl-2 expression with any of these treatments. Apoptosis was induced following 4 Gy of XRT alone, but was observed after only 2 Gy when combined with Ad5CMV-p53. Cell cycle analysis indicated that Ad5CMV-p53

  14. Recent Updates on Treatment of Ocular Microbial Infections by Stem Cell Therapy: A Review

    Directory of Open Access Journals (Sweden)

    Seoh Wei Teh

    2018-02-01

    Full Text Available Ocular microbial infection has emerged as a major public health crisis during the past two decades. A variety of causative agents can cause ocular microbial infections; which are characterized by persistent and destructive inflammation of the ocular tissue; progressive visual disturbance; and may result in loss of visual function in patients if early and effective treatments are not received. The conventional therapeutic approaches to treat vision impairment and blindness resulting from microbial infections involve antimicrobial therapy to eliminate the offending pathogens or in severe cases; by surgical methods and retinal prosthesis replacing of the infected area. In cases where there is concurrent inflammation, once infection is controlled, anti-inflammatory agents are indicated to reduce ocular damage from inflammation which ensues. Despite advances in medical research; progress in the control of ocular microbial infections remains slow. The varying level of ocular tissue recovery in individuals and the incomplete visual functional restoration indicate the chief limitations of current strategies. The development of a more extensive therapy is needed to help in healing to regain vision in patients. Stem cells are multipotent stromal cells that can give rise to a vast variety of cell types following proper differentiation protocol. Stem cell therapy shows promise in reducing inflammation and repairing tissue damage on the eye caused by microbial infections by its ability to modulate immune response and promote tissue regeneration. This article reviews a selected list of common infectious agents affecting the eye; which include fungi; viruses; parasites and bacteria with the aim of discussing the current antimicrobial treatments and the associated therapeutic challenges. We also provide recent updates of the advances in stem cells studies on sepsis therapy as a suggestion of optimum treatment regime for ocular microbial infections.

  15. Recent Updates on Treatment of Ocular Microbial Infections by Stem Cell Therapy: A Review.

    Science.gov (United States)

    Teh, Seoh Wei; Mok, Pooi Ling; Abd Rashid, Munirah; Bastion, Mae-Lynn Catherine; Ibrahim, Normala; Higuchi, Akon; Murugan, Kadarkarai; Mariappan, Rajan; Subbiah, Suresh Kumar

    2018-02-13

    Ocular microbial infection has emerged as a major public health crisis during the past two decades. A variety of causative agents can cause ocular microbial infections; which are characterized by persistent and destructive inflammation of the ocular tissue; progressive visual disturbance; and may result in loss of visual function in patients if early and effective treatments are not received. The conventional therapeutic approaches to treat vision impairment and blindness resulting from microbial infections involve antimicrobial therapy to eliminate the offending pathogens or in severe cases; by surgical methods and retinal prosthesis replacing of the infected area. In cases where there is concurrent inflammation, once infection is controlled, anti-inflammatory agents are indicated to reduce ocular damage from inflammation which ensues. Despite advances in medical research; progress in the control of ocular microbial infections remains slow. The varying level of ocular tissue recovery in individuals and the incomplete visual functional restoration indicate the chief limitations of current strategies. The development of a more extensive therapy is needed to help in healing to regain vision in patients. Stem cells are multipotent stromal cells that can give rise to a vast variety of cell types following proper differentiation protocol. Stem cell therapy shows promise in reducing inflammation and repairing tissue damage on the eye caused by microbial infections by its ability to modulate immune response and promote tissue regeneration. This article reviews a selected list of common infectious agents affecting the eye; which include fungi; viruses; parasites and bacteria with the aim of discussing the current antimicrobial treatments and the associated therapeutic challenges. We also provide recent updates of the advances in stem cells studies on sepsis therapy as a suggestion of optimum treatment regime for ocular microbial infections.

  16. Impact of hepatitis B virus infection on HIV response to antiretroviral therapy in a Chinese antiretroviral therapy center

    Directory of Open Access Journals (Sweden)

    Rongrong Yang

    2014-11-01

    Conclusions: HBV co-infection can affect late immunological and virological responses to ART and increase the risk of hepatotoxicity. Mortality due to liver disease was high among HIV/HBV co-infected individuals in this study, despite HBV-active ART. As long as HIV/HBV co-infected persons need anti-HBV therapy, they should be recommended ART that includes agents with activity against both HIV and HBV, regardless of the CD4 cell count level.

  17. Oritavancin: a new opportunity for outpatient therapy of serious infections.

    Science.gov (United States)

    Tice, Alan

    2012-04-01

    Oritavancin is a new antibiotic for the treatment of serious infections with Gram-positive bacteria. It has been shown to be effective against methicillin-susceptible and -resistant Staphylococcus aureus as well as enterococci. With a terminal half-life of 393 hours, oritavancin lends itself to a convenient and potentially cost-effective single-dose regimen. The single-dose regimen is currently being evaluated in pivotal phase 3 studies. This unique property provides an opportunity to assure consistent, effective, and safe treatment for serious infections while reducing the costs of care through the elimination of multiple infusions, reduced medical care staff, shorter hospital stays, and avoidance of hospital-acquired infections. These features seem ideal for the use of oritavancin in the outpatient management of serious infections. The impact that oritavancin will have on outpatient therapy is unclear. Current models will need to change with only a single infusion. Physician monitoring of the infection and underlying diseases may not be as frequent despite the need for close follow-up and frequent evaluations. There will be less need for a team of outpatient infusion specialists. Outpatient therapy will be compensated less without multiple infusions. With the possibility of fewer physician and other medical visits, there will be more responsibility for the patient and family and a reliance on patients to care for themselves. Although oritavancin offers tremendous theoretical advantages in the outpatient treatment of serious infections, care should be taken to assure the quality of care through changes in reimbursement, patient education, and development of systems to monitor care and outcomes.

  18. Phage therapy is effective against infection by Mycobacterium ulcerans in a murine footpad model.

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    Gabriela Trigo

    Full Text Available BACKGROUND: Buruli Ulcer (BU is a neglected, necrotizing skin disease caused by Mycobacterium ulcerans. Currently, there is no vaccine against M. ulcerans infection. Although the World Health Organization recommends a combination of rifampicin and streptomycin for the treatment of BU, clinical management of advanced stages is still based on the surgical resection of infected skin. The use of bacteriophages for the control of bacterial infections has been considered as an alternative or to be used in association with antibiotherapy. Additionally, the mycobacteriophage D29 has previously been shown to display lytic activity against M. ulcerans isolates. METHODOLOGY/PRINCIPAL FINDINGS: We used the mouse footpad model of M. ulcerans infection to evaluate the therapeutic efficacy of treatment with mycobacteriophage D29. Analyses of macroscopic lesions, bacterial burdens, histology and cytokine production were performed in both M. ulcerans-infected footpads and draining lymph nodes (DLN. We have demonstrated that a single subcutaneous injection of the mycobacteriophage D29, administered 33 days after bacterial challenge, was sufficient to decrease pathology and to prevent ulceration. This protection resulted in a significant reduction of M. ulcerans numbers accompanied by an increase of cytokine levels (including IFN-γ, both in footpads and DLN. Additionally, mycobacteriophage D29 treatment induced a cellular infiltrate of a lymphocytic/macrophagic profile. CONCLUSIONS/SIGNIFICANCE: Our observations demonstrate the potential of phage therapy against M. ulcerans infection, paving the way for future studies aiming at the development of novel phage-related therapeutic approaches against BU.

  19. A systematic review of oral fungal infections in patients receiving cancer therapy

    NARCIS (Netherlands)

    Lalla, Rajesh V.; Latortue, Marie C.; Hong, Catherine H.; Ariyawardana, Anura; D'Amato-Palumbo, Sandra; Fischer, Dena J.; Martof, Andrew; Nicolatou-Galitis, Ourania; Patton, Lauren L.; Elting, Linda S.; Spijkervet, Fred K. L.; Brennan, Michael T.

    The aims of this systematic review were to determine, in patients receiving cancer therapy, the prevalence of clinical oral fungal infection and fungal colonization, to determine the impact on quality of life and cost of care, and to review current management strategies for oral fungal infections.

  20. [Urinary tract infections : What has been confirmed in therapy?

    Science.gov (United States)

    Marcon, J; Stief, C G; Magistro, G

    2017-12-01

    Urinary tract infections (UTIs) affect approximately 150 million people worldwide per year, causing annual health costs of over three billion dollars just in the USA. Every second woman experiences at least one UTI in her lifetime, with every one in four experiencing recurrence. Uncomplicated infections like single or recurrent cystitis and pyelonephritis can be distinguished from complicated disease. UTIs in men can spread to the male glands, causing prostatitis and epididymitis. Antibiotic therapy is the standard procedure for UTIs. However, the extensive and sometimes irrational use of antibiotics for the treatment of infections has led to an increase in the incidence of multiresistant pathogens in recent years. Therefore, preventive nonantibiotic approaches are of great interest. This article provides an overview of the current management of urological infections as well as an outline of nonantibiotic preventive treatment modalities.

  1. Survival of lung cancer patients after combined therapy with hyperglycemia

    International Nuclear Information System (INIS)

    Zharkov, V.V.; Demidchik, Yu.E.; Khodina, T.V.

    1991-01-01

    The results of a randomized study of combined therapy of lung cancer patients including large field radiotherapy (total irradiation of 20 Gy, daily fractionation of 4 Gy) and induced hyperglycemia (22-23 mmol/1) are presented. The use of new variants of combined therapy was shown to increase significantly the survival of patients, however therapeutic efficacy was different depending on the time of hyperglycemia: wheter it was used before radiotherapy sessions of after their discontinuation

  2. Effect of HIV type 1 subtype on virological and immunological response to combination antiretroviral therapy: evidence for a more rapid viral suppression for subtype A than subtype B-infected Greek individuals.

    Science.gov (United States)

    Paraskevis, Dimirios; Touloumi, Giota; Bakoyannis, Giorgos; Paparizos, Vassilios; Lazanas, Marios; Gargalianos, Panagiotis; Chryssos, Georgios; Antoniadou, Anastasia; Psichogiou, Mina; Panos, Georgios; Katsarou, Olga; Sambatakou, Helen; Kordossis, Theodoros; Hatzakis, Angelos

    2013-03-01

    Whether response to combination antiretroviral therapy (cART) differs between those infected with HIV-1 subtype A or B remains unclear. We compared virological and immunological response to cART in individuals infected with subtype A or B in an ethnically homogeneous population. Data derived from the Athens Multicenter AIDS Cohort Study (AMACS) and analysis were restricted to those of Greek origin. Time to virological response (confirmed HIV-RNA 500 copies/ml at any time or no response by month 6) were analyzed using survival models and CD4 changes after cART initiation using piecewise linear mixed effects models. Of the 571 subjects included in the analysis, 412 (72.2%) were infected with subtype B and 159 (27.8%) with subtype A. After adjusting for various prognostic factors, the rate of virological response was higher for those infected with subtype A versus B (adjusted HR: 1.35; 95% CI: 1.08-1.68; p=0.009). Subtype A was also marginally associated with a lower hazard of virological failure compared to subtype B (HR=0.73; 95% CI: 0.53-1.02; p=0.062). Further adjustment for treatment adherence did not substantially changed the main results. No significant differences were observed in the rates of CD4 increases by subtype. The overall median (95% CI) CD4 increase at 2 years of cART was 193 (175, 212) cells/μl. Our study, based on one of the largest homogeneous groups of subtype A and B infections in Europe, showed that individuals infected with subtype A had an improved virological but similar immunological response to cART compared to those infected with subtype B.

  3. Impact of Extended Combination Antiretroviral Therapy on the Decline of HIV Prevalence in Pregnant Women in Malawi.

    Science.gov (United States)

    Liotta, Giuseppe; Chimbwandira, Frank; Wouters, Kristien; Nielsen-Saines, Karin; Jere, Haswell; Mancinelli, Sandro; Ceffa, Susanna; Erba, Fulvio; Palombi, Leonardo; Marazzi, Maria Cristina

    2016-01-01

    Combination antiretroviral therapy has been shown to reduce HIV transmission and incident infections. In recent years, Malawi has significantly increased the number of individuals on combination antiretroviral drugs through more inclusive treatment policies. Using a retrospective observational cohort design, records with HIV test results were reviewed for pregnant women attending a referral hospital in Malawi over a 5-year period, with viral load measurements recorded. HIV prevalence over time was determined, and results correlated with population viral load. A total of 11 052 women were included in this analysis, with 440 (4.1%) HIV infections identified. HIV prevalence rates in pregnant women in Malawi halved from 6.4% to 3.0% over 5 years. Mean viral loads of adult patients decreased from 120 000 copies/mL to less than 20 000 copies/mL. Results suggest that community viral load has an effect on HIV incidence rates in the population, which in turn correlates with reduced HIV prevalence rates in pregnant women. © The Author(s) 2015.

  4. Gastrointestinal Toxicities With Combined Antiangiogenic and Stereotactic Body Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Pollom, Erqi L.; Deng, Lei [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Pai, Reetesh K. [Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (United States); Brown, J. Martin; Giaccia, Amato; Loo, Billy W.; Shultz, David B.; Le, Quynh Thu; Koong, Albert C. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Chang, Daniel T., E-mail: dtchang@stanford.edu [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States)

    2015-07-01

    Combining the latest targeted biologic agents with the most advanced radiation technologies has been an exciting development in the treatment of cancer patients. Stereotactic body radiation therapy (SBRT) is an ablative radiation approach that has become established for the treatment of a variety of malignancies, and it has been increasingly used in combination with biologic agents, including those targeting angiogenesis-specific pathways. Multiple reports have emerged describing unanticipated toxicities arising from the combination of SBRT and angiogenesis-targeting agents, particularly of late luminal gastrointestinal toxicities. In this review, we summarize the literature describing these toxicities, explore the biological mechanism of action of toxicity with the combined use of antiangiogenic therapies, and discuss areas of future research, so that this combination of treatment modalities can continue to be used in broader clinical contexts.

  5. Increased virological failure in naive HIV-1-infected patients taking lamivudine compared with emtricitabine in combination with tenofovir and efavirenz or nevirapine in the Dutch nationwide ATHENA cohort

    NARCIS (Netherlands)

    Rokx, C.; Fibriani, A.; Vijver, D.A. van de; Verbon, A.; Schutten, M.; Gras, L.; Rijnders, B.J.; Koopmans †, P.P.; Keuter, M.; Ven, A.J.A.M. van der; Hofstede, H.J.M. ter; Dofferhoff, A.S.M.; Warris, A.; Crevel, R. van; et al.,

    2015-01-01

    BACKGROUND: Guidelines for treatment of human immunodeficiency virus type 1 (HIV-1) infection consider lamivudine and emtricitabine to be interchangeable components in first-line combination antiretroviral therapy (cART). The evidence for their clinical equivalence in cART is inconsistent. The

  6. Modern approaches to parodontitis therapy in HIV patients

    Directory of Open Access Journals (Sweden)

    Shuldyakov A.A.

    2011-12-01

    Full Text Available The research goal is to determine the clinical pathogenetic efficacy of Cycloferon liniment in the combined therapy of periodontitis in patients with subclinical stage of HIV-infection. Medical examination and treatment of 40 patients has been carried out. It is established that use of liniment Cycloferon in the combined treatment of patients with subclinical stage of HIV-infection allows to accelerate process of normalization of lipid peroxidation parameters and antioxidant potential of blood and to decrease infection (herpes symplex virus I, Candida albicans, staphylococcus aureus in par-odontal recess and evidence of local inflammation. The considered method of therapy has been proved to improve convalescence period and to decrease frequency of parodontitis recurrences

  7. Combinational chelation therapy abrogates lead-induced neurodegeneration in rats

    International Nuclear Information System (INIS)

    Pachauri, Vidhu; Saxena, Geetu; Mehta, Ashish; Mishra, Deepshikha; Flora, Swaran J.S.

    2009-01-01

    Lead, a ubiquitous and potent neurotoxicant causes oxidative stress which leads to numerous neurobehavioral and physiological alterations. The ability of lead to bind sulfhydryl groups or compete with calcium could be one of the reasons for its debilitating effects. In the present study, we addressed: i) if chelation therapy could circumvent the altered oxidative stress and prevent neuronal apoptosis in chronic lead-intoxicated rats, ii) whether chelation therapy could reverse biochemical and behavioral changes, and iii) if mono or combinational therapy with captopril (an antioxidant) and thiol chelating agents (DMSA/MiADMSA) is more effective than individual thiol chelator in lead-exposed rats. Results indicated that lead caused a significant increase in reactive oxygen species, nitric oxide, and intracellular free calcium levels along with altered behavioral abnormalities in locomotor activity, exploratory behavior, learning, and memory that were supported by changes in neurotransmitter levels. A fall in membrane potential, release of cytochrome c, and DNA damage indicated mitochondrial-dependent apoptosis. Most of these alterations showed significant recovery following combined therapy with captopril with MiADMSA and to a smaller extend with captopril + DMSA over monotherapy with these chelators. It could be concluded from our present results that co-administration of a potent antioxidant (like captopril) might be a better treatment protocol than monotherapy to counter lead-induced oxidative stress. The major highlight of the work is an interesting experimental evidence of the efficacy of combinational therapy using an antioxidant with a thiol chelator in reversing neurological dystrophy caused due to chronic lead exposure in rats.

  8. Comorbidity and ageing in HIV infection

    NARCIS (Netherlands)

    Kooij, K.W.

    2017-01-01

    In the era of modern combination antiretroviral therapy (cART) the HIV-infected population is ageing. Studies have suggested that HIV-infected individuals, even if appropriately treated with cART, may be at increased risk for several age-related conditions. In this thesis a variety of age-related

  9. Antiviral T Cells for Adenovirus in the Pretransplant Period: A Bridge Therapy for Severe Combined Immunodeficiency.

    Science.gov (United States)

    Miller, Holly K; Hanley, Patrick J; Lang, Haili; Lazarski, Christopher A; Chorvinsky, Elizabeth A; McCormack, Sarah; Roesch, Lauren; Albihani, Shuroug; Dean, Marcus; Hoq, Fahmida; Adams, Roberta H; Bollard, Catherine M; Keller, Michael D

    2018-05-09

    Viral infections can be life threatening in patients with severe combined immunodeficiency (SCID) and other forms of profound primary immunodeficiency disorders both before and after hematopoietic stem cell transplantation (HSCT). Adoptive immunotherapy with virus-specific T cells (VSTs) has been utilized in many patients in the setting of HSCT, but has very rarely been attempted for treatment of viral infections before HSCT. Here we describe the use of VSTs in an infant with RAG1 SCID who had developed disseminated adenovirus which failed to improve on cidofovir. Adenovirus cleared following 2 doses of VSTs and marrow infusion from a matched unrelated donor, without incidence of graft versus host disease. T cell receptor-b sequencing demonstrated expansion of adenovirus-specific T cell fraction of the VSTs, suggesting that infusion facilitated viral clearance. This report suggests that VSTs are likely safe in the pre-HSCT period, and may be a useful bridge therapy for infants with SCID and persistent viral infections. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  10. A Systematic Review of Clinical Practice Guidelines' Recommendations on Levothyroxine Therapy Alone versus Combination Therapy (LT4 plus LT3) for Hypothyroidism.

    Science.gov (United States)

    Kraut, Eyal; Farahani, Pendar

    2015-12-04

    Patients with hypothyroidism are increasingly enquiring about the benefit of using combination therapy of levothyroxine (LT4) and liothyronine (LT3) as a potential treatment for hypothyroidism. Combination therapy, however, remains controversial. The purpose of this study was to systematically review available hypothyroidism treatment recommendations from clinical practice guidelines from around the world to identify the consensus regarding combination therapy. Clinical practice guidelines were obtained from searches of PubMed, EMBASE, and MEDLINE, using several combinations of MeSH terms. The search was limited to clinical guidelines in English-language publications, published between January 1, 1990 and May 1, 2015. A quantitative approach was utilized for data synthesis. Thirteen guidelines were identified, including three regarding pregnancy, two regarding pediatric populations and eight regarding adult populations. There were six guidelines from North America, four guidelines from Europe and three guidelines from South America. Twelve of the guidelines were published after 2010. Nine guidelines addressed combination therapy of LT4 plus LT3, and all nine concluded that LT4 therapy alone is the standard of care, with insufficient evidence to recommend widespread combination therapy. Only the 2012 ETA Guidelines and the 2015 BTA Guidelines concluded that combination therapy could be used, although only in certain circumstances and as an experimental treatment. This systematic review illustrates that clinical practice guidelines worldwide do not recommend and do not support routine use of combination LT4 and LT3 therapy to treat hypothyroidism.

  11. Combination therapy for hepatitis C virus with heat-shock protein 90 inhibitor 17-AAG and proteasome inhibitor MG132.

    Science.gov (United States)

    Ujino, Saneyuki; Yamaguchi, Saori; Shimotohno, Kunitada; Takaku, Hiroshi

    2010-03-09

    Hepatitis C virus (HCV) infection is a major cause of chronic liver disease. Here, we report a new and effective strategy for inhibiting HCV replication using an inhibitor of heat-shock protein 90, 17-AAG (17-allylamino-17demethoxygeldanamycin), and a proteasome inhibitor, MG132. To explore the virological basis of combination therapy, we analysed the effects of 17-AAG and MG132, singly and in combination on HCV replication in an HCV replicon cell system. In HCV replicon cells, HCV RNA replication was suppressed by 17-AAG in a dose-dependent manner. As shown in the present study, the 50% inhibitory concentration values were 0.82 nM for 17-AAG and 0.21 nM for MG132. Low concentrations of MG132 had strong synergistic inhibitory effects with low toxicity on HCV replicon cells. The results of this study suggest that the different effects and synergistic actions of 17-AAG and MG132 could provide a new therapeutic approach to HCV infection.

  12. ZTI-01 Treatment Improves Survival of Animals Infected with Multidrug Resistant Pseudomonas aeruginosa

    Science.gov (United States)

    Lawrenz, Matthew B; denDekker, Ashley Eb; Cramer, Daniel E; Gabbard, Jon D; Lafoe, Kathryn M; Pfeffer, Tia L; Sotsky, Julie B; Vanover, Carol D; Ellis-Grosse, Evelyn J; Warawa, Jonathan M

    2017-01-01

    Abstract Background ZTI-01 (fosfomycin, FOS, for injection) is currently under US development to treat complicated urinary tract infections. ZTI-01 is unique compared with other antimicrobials in that it inhibits an early step in cell wall synthesis via covalent binding to MurA. ZTI-01 demonstrates broad in vitro activity against Gram-negative (GN) and -positive (GP) bacteria, including multidrug-resistant (MDR) organisms. Our study goals were to determine the efficacy of ZTI-01 as a monotherapy or in combination with meropenem against MDR Pseudomonas aeruginosa in a preclinical model of pulmonary infection. Methods 8 week old neutropenic mice were infected with a MDR strain of P. aeruginosa via intubation-mediated intratracheal (IMIT) instillation. 3 hours after instillation, mice received treatment with ZTI-01, meropenem, or ZTI-01 plus meropenem (combination therapy) q8h for 5 days. Mice were monitored every 8 hours for 7 days for development of disease and moribund animals were humanely euthanized. Lungs and spleens were harvested at euthanasia, or at 7 days for survivors, and processed for bacterial enumeration and development of pathology. Results Mice were challenged with a lethal dose of P. aeruginosa UNC-D. Mock treated animals succumbed to infection within 36 hours post-infection. Animals that received 6 g/kg/day ZTI-01 showed an increase in the MTD (52 hours) and 25% of the cohort were protected from lethal disease. Combining ZTI-01 with meropenem resulted in a significant increase in survival (≥75% of cohorts survived infection). Combination therapy also significantly decreased bacterial numbers in the lungs and inhibited dissemination to the spleens. Furthermore, animals receiving combination therapy were protected from significant inflammation in the lungs and the development of pneumonia. Conclusion Here we report that combination therapy with ZTI-01 and meropenem provides significant improvements in all disease manifestations over treatment with

  13. Oral combination therapy: repaglinide plus metformin for treatment of type 2 diabetes.

    Science.gov (United States)

    Raskin, P

    2008-12-01

    Type 2 diabetes is characterized by decreases in insulin secretion and insulin sensitivity. Several classes of oral antidiabetic medications are currently approved for the treatment of type 2 diabetes. A stepwise treatment approach from monotherapy to combination therapy is traditionally used; however, the frequency of treatment failure with monotherapy has resulted in a move towards earlier treatment with combination therapies that target the two principal defects in glycaemic control. One such combination regimen is repaglinide (a prandial glucose regulator that increases insulin release) plus metformin (an insulin sensitizer that inhibits hepatic glucose output, increases peripheral glucose uptake and utilization and minimizes weight gain). Findings from several clinical trials have shown that combination therapy with repaglinide plus metformin is well tolerated and results in greater reductions of haemoglobin A(1c) and fasting plasma glucose values compared with either monotherapy. Repaglinide may also provide a more suitable alternative to combination therapy with sulphonylureas and metformin because of its reduced propensity for hypoglycaemia. The combination regimen of repaglinide plus metformin should therefore be considered as a valuable option in the management of patients with type 2 diabetes when monotherapy is no longer adequate.

  14. Follicular bronchiolitis in an HIV-infected individual on combination antiretroviral therapy with low CD4+ cell count but sustained viral suppression

    DEFF Research Database (Denmark)

    Rasmussen, Line D; Pedersen, Court; Madsen, Helle D

    2017-01-01

    A 36-year-old Danish man, living in Asia, was diagnosed with Pneumocystis pneumonia (PCP) and HIV in 2013 (CD4+ count: 6 cells/µL; viral load: 518 000 copies/mL). He initiated combination antiretroviral therapy. Later that year, he was also diagnosed with granulomatosis with polyangiitis and was ......A 36-year-old Danish man, living in Asia, was diagnosed with Pneumocystis pneumonia (PCP) and HIV in 2013 (CD4+ count: 6 cells/µL; viral load: 518 000 copies/mL). He initiated combination antiretroviral therapy. Later that year, he was also diagnosed with granulomatosis with polyangiitis...... tests demonstrated severely reduced lung capacity with an obstructive pattern and a moderately reduced diffusion capacity. High resolution computer tomography revealed minor areas with tree-in-bud pattern and no signs of air trapping on expiratory views. Lung biopsy showed lymphocytic infiltration...

  15. Therapeutic potential of and treatment with boceprevir/telaprevir-based triple-therapy in HIV/chronic hepatitis C co-infected patients in a real-world setting.

    Science.gov (United States)

    Mandorfer, Mattias; Payer, Berit A; Niederecker, Alexander; Lang, Gerold; Aichelburg, Maximilian C; Strassl, Robert; Boesecke, Christoph; Rieger, Armin; Trauner, Michael; Peck-Radosavljevic, Markus; Reiberger, Thomas

    2014-05-01

    The aim of this study was to assess the therapeutic potential of telaprevir (TPV)/boceprevir (BOC)-based triple-therapy in a complete cohort of HIV/chronic hepatitis C co-infected patients (HIV/HCV). Moreover, a case series of four HIV/HCV genotype (HCV-GT)1 patients with rapid virologic response (RVR), who received only 28 weeks of BOC-based triple-therapy (BOCW28), was reported. 290/440 HIV-positive patients with positive HCV serology had at least one visit during the past 2 years, 142/290 had target detectable HCV-RNA with 64% (82/142) carrying HCV-GT1. While 18 HIV/HCV-GT1 displayed contraindications, 45% (64/142) of HIV/HCV were eligible for triple-therapy. Insufficiently controlled HIV-infection despite combined antiretroviral therapy (cART) (HIV-RNA treatment uptake rates (39% (25/64)) during the first 2 years of triple-therapy availability suggest that its benefit in HIV/HCV co-infected patients might fall short of expectations. Modification of cART or TPV dose adjustment would have been necessary in 61% and 84% of HIV/HCV-GT1 on cART eligible for triple-therapy using TPV and BOC, respectively, suggesting that drug-drug interactions with cART complicate management in the majority of patients. All four BOCW28 patients achieved a sustained virologic response. Prospective studies are necessary to validate our observations on the shortening of treatment duration in HIV/HCV-GT1 with RVR.

  16. In vitro activity of colistin mono- and combination therapy against colistin-resistant Acinetobacter baumannii, mechanism of resistance, and clinical outcomes of patients infected with colistin-resistant A. baumannii at a Thai university hospital

    Directory of Open Access Journals (Sweden)

    Lertsrisatit Y

    2017-11-01

    Full Text Available Yongyut Lertsrisatit,1 Wichai Santimaleeworagun,2,3 Sudaluck Thunyaharn,4 Jantima Traipattanakul5 1College of Pharmacotherapy Thailand, Nonthaburi, Thailand; 2Department of Pharmacy, Faculty of Pharmacy, Silpakorn University, Nakorn Pathom, Thailand; 3Pharmaceutical Initiative for Resistant Bacteria and Infectious Diseases Working Group (PIRBIG Faculty of Pharmacy, Silpakorn University, Nakorn Pathom, Thailand; 4Faculty of Medical Technology, Nakhonratchasima College, Nakhonratchasima, Thailand; 5Division of Infectious Disease, Department of Medicine, Phramongkutklao Hospital, Bangkok, Thailand Purpose: Colistin is a drug of last resort for treating multidrug-resistant Acinetobacter baumannii infections. Unfortunately, colistin-resistant A. baumannii (CoR-AB has been reported. Here, we examined the in vitro effect of mono- and combined antimicrobials against CoR-AB strains and their resistance mechanism, and evaluated the clinical outcomes of CoR-AB-infected patients.Patients and methods: Seventeen clinical CoR-AB strains were isolated from patients at Phramongkutklao hospital, 2011–2015. The mono- and synergistic activities of colistin, tigecycline, sulbactam, imipenem, meropenem, amikacin, fosfomycin, and cotrimoxazole were examined by minimum inhibitory concentration (MIC and fractional inhibitory concentration index. Clonal relationship and resistance genes were determined by repetitive extragenic palindromic polymerase chain reaction with specific primers. The effect of carbonyl cyanide 3-chlorophenylhydrazone combined with colistin was used to test efflux pump involvement. Patient treatment outcomes were also reported.Results: The most prevalent infection in CoR-AB patients was pneumonia (35.3%, and all patients were administered colistin combined with another agent. The 30-day mortality was 70.6%, and the colistin MIC range and MIC50 was 16–512 µg/mL and 64 µg/mL, respectively. All CoR-AB strains were sensitive to tigecycline

  17. Baseline prediction of combination therapy outcome in hepatitis C virus 1b infected patients by discriminant analysis using viral and host factors.

    Science.gov (United States)

    Saludes, Verónica; Bracho, Maria Alma; Valero, Oliver; Ardèvol, Mercè; Planas, Ramón; González-Candelas, Fernando; Ausina, Vicente; Martró, Elisa

    2010-11-30

    Current treatment of chronic hepatitis C virus (HCV) infection has limited efficacy -especially among genotype 1 infected patients-, is costly, and involves severe side effects. Thus, predicting non-response is of major interest for both patient wellbeing and health care expense. At present, treatment cannot be individualized on the basis of any baseline predictor of response. We aimed to identify pre-treatment clinical and virological parameters associated with treatment failure, as well as to assess whether therapy outcome could be predicted at baseline. Forty-three HCV subtype 1b (HCV-1b) chronically infected patients treated with pegylated-interferon alpha plus ribavirin were retrospectively studied (21 responders and 22 non-responders). Host (gender, age, weight, transaminase levels, fibrosis stage, and source of infection) and viral-related factors (viral load, and genetic variability in the E1-E2 and Core regions) were assessed. Logistic regression and discriminant analyses were used to develop predictive models. A "leave-one-out" cross-validation method was used to assess the reliability of the discriminant models. Lower alanine transaminase levels (ALT, p=0.009), a higher number of quasispecies variants in the E1-E2 region (number of haplotypes, nHap_E1-E2) (p=0.003), and the absence of both amino acid arginine at position 70 and leucine at position 91 in the Core region (p=0.039) were significantly associated with treatment failure. Therapy outcome was most accurately predicted by discriminant analysis (90.5% sensitivity and 95.5% specificity, 85.7% sensitivity and 81.8% specificity after cross-validation); the most significant variables included in the predictive model were the Core amino acid pattern, the nHap_E1-E2, and gamma-glutamyl transferase and ALT levels. Discriminant analysis has been shown as a useful tool to predict treatment outcome using baseline HCV genetic variability and host characteristics. The discriminant models obtained in this

  18. The use of negative pressure wound therapy in the treatment of infected wounds. Case studies

    Directory of Open Access Journals (Sweden)

    Daniel de Alcântara Jones

    Full Text Available ABSTRACT OBJECTIVE: To evaluate the results and benefits obtained from the topical use of negative pressure wound therapy (NPWT in patients with infected wounds. METHODS: This was a retrospective study of 20 patients (17 males and three females, mean age 42 years with infected wounds treated using NPWT. The infected wounds were caused by trauma. The treatment system used was VAC.(r (Vacuum Assisted Closure, KCI, San Antonio, United States applied to the wound in continuous mode from 100 to 125 mmHg. The parameters related to the wounds (location, number of VAC changes, the size of the defects in the soft parts, and the evolution of the state of the wound, length of hospital stay, length of intravenous antibiotic therapy, and complications related to the use of this therapy were evaluated. RESULTS: The mean length of the hospital stay, use of NPWT, and antibacterial therapy were 41 days, 22.5 days, and 20 days respectively. The use of the VAC led to a mean reduction of 29% in the wound area (95.65-68.1 cm2; p < 0.05. Only one patient did not show any improvement in the final appearance of the wound with complete eradication of the infection. No complication directly caused by NPWT was observed. CONCLUSION: NPWT stimulates infection-free scar tissue formation in a short time, and is a quick and comfortable alternative to conventional infected wounds treatment methods.

  19. NEW POSSIBILITIES OF STAPHYLOCOCC INFECTION THERAPY

    Directory of Open Access Journals (Sweden)

    M. V. Matyushkina

    2014-12-01

    Full Text Available Introduction. Staphylococcus cause wide range of diseases ranging from mild skin infections to severe neuroinfections. So far, it is one of the four most common causes of nosocomial infections. Emergence and widespread resistance to various forms of medicines for staphylococci is more characteristic than for any other bacteria species. Therefore there is a need to develop new drugs to combat the pathogen, which can be used for effective treatment of infections caused by Staphylococcus aureus. At the Department of General Chemistry and Polymers Odessa I.I. Mechnikov National University different metal (Mg, Co bis (citrate germanates (stanates - coordination compounds have been synthesized. Their molecules contain three bioactive components, such as citric acid residue (H4Citr; ions Ge4+ or Sn4+; Mg2+ or Co2+: [Mg(H2O6][Ge(HCitr2]·4H2O (germacit; [Co(H2O6][Ge(HCitr2]·4H2O (gercocit; [Mg(H2O6][Sn(HCitr2]·4H2O (stanmacit; [Co(H2O6][Sn(HCitr2]·4H2O (stancocit. Screening studies have shown that these compounds have neurotropic properties and both show antistaphylococcal activity. The aim of research is the investigation of influence of new coordinative metal compounds, namely germacit, gercocit, stanmacit and stancocit on Staphylococcus aureus different strains’ growth in case of their separate and combined administration with benzylpenicillin-sodium on nutrient broth. Materials and methods. Experiments were performed on Staphylococcus aureus АТСС 25923, Staphylococcus aureus 2781, Staphylococcus aureus Kunda strains. We determined minimal inhibitory concentration (MIC for metal complexes, benzylpenicillin sodium and antibacterial activity in the joint application of biologically active compounds at the same concentrations and benzylpenicillin sodium (BPN in nutrient broth. Results’ accounting was performed using the values of optical density slurries in units of Mac Farland (McF. Experiments were carried out 3-5 reps. Results were treated

  20. Immediate Initiation of Antiretroviral Therapy for HIV Infection Accelerates Bone Loss Relative to Deferring Therapy

    DEFF Research Database (Denmark)

    Hoy, Jennifer F; Grund, Birgit; Roediger, Mollie P

    2017-01-01

    Both HIV infection and antiretroviral therapy (ART) are associated with lower bone mineral density (BMD) and increased fracture risk. Because the relative contributions of ART and untreated HIV to BMD loss are unclear, it is important to quantify the effect of ART on bone. We compared the effect ...

  1. Low Prolactin and High 20-α-Hydroxysteroid Dehydrogenase Levels Contribute to Lower Progesterone Levels in HIV-Infected Pregnant Women Exposed to Protease Inhibitor-Based Combination Antiretroviral Therapy.

    Science.gov (United States)

    Papp, Eszter; Balogun, Kayode; Banko, Nicole; Mohammadi, Hakimeh; Loutfy, Mona; Yudin, Mark H; Shah, Rajiv; MacGillivray, Jay; Murphy, Kellie E; Walmsley, Sharon L; Silverman, Michael; Serghides, Lena

    2016-05-15

    It has been reported that pregnant women receiving protease inhibitor (PI)-based combination antiretroviral therapy (cART) have lower levels of progesterone, which put them at risk of adverse birth outcomes, such as low birth weight. We sought to understand the mechanisms involved in this decline in progesterone level. We assessed plasma levels of progesterone, prolactin, and lipids and placental expression of genes involved in progesterone metabolism in 42 human immunodeficiency virus (HIV)-infected and 31 HIV-uninfected pregnant women. In vitro studies and a mouse pregnancy model were used to delineate the effect of HIV from that of PI-based cART on progesterone metabolism. HIV-infected pregnant women receiving PI-based cART showed a reduction in plasma progesterone levels (P= .026) and an elevation in placental expression of the progesterone inactivating enzyme 20-α-hydroxysteroid dehydrogenase (20α-HSD; median, 2.5 arbitrary units [AU]; interquartile range [IQR], 1.00-4.10 AU), compared with controls (median, 0.89 AU; IQR, 0.66-1.26 AU;P= .002). Prolactin, a key regulator of 20α-HSD, was lower (P= .012) in HIV-infected pregnant women. We observed similar data in pregnant mice exposed to PI-based cART. In vitro inhibition of 20α-HSD activity in trophoblast cells reversed PI-based cART-induced decreases in progesterone levels. Our data suggest that the decrease in progesterone levels observed in HIV-infected pregnant women exposed to PI-based cART is caused, at least in part, by an increase in placental expression of 20α-HSD, which may be due to lower prolactin levels observed in these women. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  2. Domestic dengue infection with hemophagocytic lymphohistiocytosis successfully treated by early steroid therapy.

    Science.gov (United States)

    Yoshifuji, Kota; Oshina, Takahiro; Sonokawa, Saeko; Noguchi, Yuma; Suzuki, Sayaka; Tanaka, Keisuke; Kumagai, Takashi

    2016-07-01

    A 34-year-old man, working at a park in Tokyo, Japan, was repeatedly bitten by mosquitoes while cutting grass. He was hospitalized with sudden fever, fatigue, and weakness. He was eventually diagnosed with dengue virus infection, detected using reverse transcription polymerase chain reaction for the genome and by the presence of nonstructural protein 1 in his peripheral blood. Symptomatic treatments such as acetaminophen for the fever were not effective. Moreover, peripheral blood examination showed drastically decreased white blood cells and platelets, as well as marked elevations of ferritin and soluble interleukin 2 receptor. Furthermore, bone marrow examination revealed increased macrophages with hemophagocytosis. Dengue infection with hemophagocytic lymphohistiocytosis (HLH) was ultimately diagnosed. Half-dose steroid pulse therapy for three days dramatically reduced his temperature, thereby ameliorating physical symptoms and restoring normal peripheral blood data. He was discharged 12 days after admission. Dengue infection with HLH is rare and this is the first report, to our knowledge, of domestic dengue infection with HLH in Japan. Early steroid therapy may be effective in such cases.

  3. Reference curves for CD4 T-cell count response to combination antiretroviral therapy in HIV-1-infected treatment-naïve patients.

    Science.gov (United States)

    Bouteloup, V; Sabin, C; Mocroft, A; Gras, L; Pantazis, N; Le Moing, V; d'Arminio Monforte, A; Mary-Krause, M; Roca, B; Miro, J M; Battegay, M; Brockmeyer, N; Berenguer, J; Morlat, P; Obel, N; De Wit, S; Fätkenheuer, G; Zangerle, R; Ghosn, J; Pérez-Hoyos, S; Campbell, M; Prins, M; Chêne, G; Meyer, L; Dorrucci, M; Torti, C; Thiébaut, R

    2017-01-01

    The aim of this work was to provide a reference for the CD4 T-cell count response in the early months after the initiation of combination antiretroviral therapy (cART) in HIV-1-infected patients. All patients in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) cohort who were aged ≥ 18 years and started cART for the first time between 1 January 2005 and 1 January 2010 and who had at least one available measurement of CD4 count and a viral load ≤ 50 HIV-1 RNA copies/mL at 6 months (± 3 months) after cART initiation were included in the study. Unadjusted and adjusted references curves and predictions were obtained using quantile regressions. A total of 28 992 patients were included in the study. The median CD4 T-cell count at treatment initiation was 249 [interquartile range (IQR) 150, 336] cells/μL. The median observed CD4 counts at 6, 9 and 12 months were 382 (IQR 256, 515), 402 (IQR 274, 543) and 420 (IQR 293, 565) cells/μL. The two main factors explaining the variation of CD4 count at 6 months were AIDS stage and CD4 count at cART initiation. A CD4 count increase of ≥ 100 cells/mL is generally required in order that patients stay 'on track' (i.e. with a CD4 count at the same percentile as when they started), with slightly higher gains required for those starting with CD4 counts in the higher percentiles. Individual predictions adjusted for factors influencing CD4 count were more precise. Reference curves aid the evaluation of the immune response early after antiretroviral therapy initiation that leads to viral control. © 2016 British HIV Association.

  4. Efficacy of intense pulse light therapy and tripple combination cream versus intense pulse light therapy and tripple combination cream alone in epidermal melasma treatment

    International Nuclear Information System (INIS)

    Shakeeb, N.; Noor, S.M.; Paracha, M.M.; Ullah, G.

    2018-01-01

    Objective:To compare the efficacy of intense pulse light therapy (IPL) and triple combination cream (TCC) versus intense pulse light therapy and triple combination cream alone in epidermal melasma treatment, downgrading MASI score to more than 10. Study Design:Randomized controlled trial. Place and Duration of Study:Dermatology Department, Lady Reading Hospital, Peshawar, from August 2014 to January 2015. Methodology:Patients of 18-45 years were included in the study with Fitzpatrick skin type II-V. Sample of 96 patients was divided in to three groups of 32 each, through consecutive (non-probability) sampling method. Detailed history was taken, Woods Lamp Examination done, and melasma area and severity index (MASI) score was calculated. TCC had to be applied daily at night for two months by group A patients while group B was consigned for IPL therapy fortnightly, and those in group C were given both for two months. Efficacy was compared by recalculating MASI score at treatment end as well as at follow-up after 4 weeks, using Chi-square test with significance at p < 0.05. Results:Male and female patients were 10 (31.2%) and 22 (68.8%) in group A, 7 (21.9%) and 25 (78.1%) in group B, while in group C were 12 (37.5%) and 20 (62.5%). The average age was 28.70 +8.70 years. MASI score reduction was achieved in 22 (68.8%) patients in group A; whereas, in 20 (62.5%) and 30(93.8%) patients in group B and C, respectively. Efficacy-wise distribution was significant (p=0.009). Conclusion:Intense pulse light therapy and triple combination cream are more efficacious in epidermal melasma treatment than intense pulse light therapy and triple combination cream alone. (author)

  5. The combination of amoxicillin-clavulanic acid and ketoconazole in the treatment of Madurella mycetomatis eumycetoma and Staphylococcus aureus co-infection.

    Directory of Open Access Journals (Sweden)

    Najwa A Mhmoud

    2014-06-01

    Full Text Available Eumycetoma is a chronic progressive disabling and destructive inflammatory disease which is commonly caused by the fungus Madurella mycetomatis. It is characterized by the formation of multiple discharging sinuses. It is usually treated by antifungal agents but it is assumed that the therapeutic efficiency of these agents is reduced by the co-existence of Staphylococcus aureus co-infection developing in these sinuses. This prospective study was conducted to investigate the safety, efficacy and clinical outcome of combined antibiotic and antifungal therapy in eumycetoma patients with superimposed Staphylococcus aureus infection. The study enrolled 337 patients with confirmed M. mycetomatis eumycetoma and S. aureus co-infection. Patients were allocated into three groups; 142 patients received amoxicillin-clavulanic acid and ketoconazole, 93 patients received ciprofloxacin and ketoconazole and 102 patients received ketoconazole only. The study showed that, patients who received amoxicillin-clavulanic acid and ketoconazole treatment had an overall better clinical outcome compared to those who had combined ciprofloxacin and ketoconazole or to those who received ketoconazole only. In this study, 60.6% of the combined amoxicillin-clavulanic acid/ketoconazole group showed complete or partial clinical response to treatment compared to 30.1% in the ciprofloxacin/ketoconazole group and 36.3% in the ketoconazole only group. The study also showed that 64.5% of the patients in the ciprofloxacin/ketoconazole group and 59.8% in the ketoconazole only group had progressive disease and poor outcome. This study showed that the combination of amoxicillin-clavulanic acid and ketoconazole treatment is safe and offers good clinical outcome and it is therefore recommended to treat eumycetoma patients with Staphylococcus aureus co-infection.

  6. Experimental study of chemical embolus therapy combined with radiotherapy for VX2 bone tumors

    International Nuclear Information System (INIS)

    Yamaguchi, Hiroshi; Mochizuki, Kazuo; Ishii, Yoshiaki

    2000-01-01

    We conducted an experimental study, using a combination of coarse crystal cisplatin and radiotherapy for bone tumors, to evaluate the possibility of the clinical application of chemical embolus therapy in the field of orthopedic surgery. Experimental femoral bone tumors were produced, in rabbits, using VX2 carcinoma. The rabbits were allocated to five groups: untreated control, embolus, chemical embolus, irradiation alone, and chemical embolus and irradiation combination. These therapies were evaluated comparatively, in terms of local antitumor effects (including body weight, X-ray findings, angiography, and histopathology) and in terms of inhibition of pulmonary metastasis. Local antitumor effects, as evaluated by all parameters, except for body weight, were significantly greater for the chemical and irradiation combination group than for the chemical embolus, irradiation alone, untreated control, and embolus groups. There was no significant difference in the inhibition of pulmonary metastasis among the chemical embolus and irradiation combination, chemical embolus, and irradiation alone groups. These findings demonstrated the synergistic effect of the combination of chemical embolus therapy and radiotherapy. In this study, however, no significant difference was found between the chemical embolus therapy alone and the combination therapy groups in the inhibitory effect on pulmonary tumor metastasis, suggesting the need to conduct combination therapy repeatedly in the clinical setting. (author)

  7. Atorvastatin/trimetazidine combination therapy in patients with ...

    African Journals Online (AJOL)

    Purpose: To explore the outcomes and safety of atorvastatin/trimetazidine combination therapy in patients with chronic cardiac failure. Methods: A total of 144 patients with chronic cardiac failure were divided into test group (n = 72) and control group (n = 72). In addition to conventional anti-heart failure treatment, all patients ...

  8. The impact of fixed-dose combination versus free-equivalent combination therapies on adherence for hypertension: a meta-analysis.

    Science.gov (United States)

    Du, Li-Ping; Cheng, Zhong-Wei; Zhang, Yu-Xuan; Li, Ying; Mei, Dan

    2018-04-27

    Nonadherence to antihypertensive medication is considered as a reason of inadequate control of blood pressure. This meta-analysis aimed to systemically evaluate the impact of fixed-dose combination (FDC) therapy on hypertensive medication adherence compared with free-equivalent combination therapies. Articles were retrieved from MEDLINE and Embase databases using a combination of terms "fixed-dose combinations" and "adherence or compliance or persistence" and "hypertension or antihypertensive" from January 2000 to June 2017 without any language restriction. A meta-analysis was performed to parallel compare the impact of FDC vs free-equivalent combination on medicine adherence or persistence. Studies were independently reviewed by two investigators. Data from eligible studies were extracted and a meta-analysis was performed using R version 3.1.0 software. A total of nine studies scored as six of nine to eight of nine for Newcastle-Ottawa rating with 62 481 patients with hypertension were finally included for analysis. Results showed that the mean difference of medication adherence for FDC vs free-equivalent combination therapies was 14.92% (95% confidence interval, 7.38%-22.46%). Patients in FDC group were more likely to persist with their antihypertensive treatment, with a risk ratio of 1.84 (95% confidence interval, 1.00-3.39). This meta-analysis confirmed that FDC therapy, compared with free-equivalent combinations, was associated with better medication adherence or persistence for patients with hypertension. It can be reasonable for physicians, pharmacists, and policy makers to facilitate the use of FDCs for patients who need to take two or more antihypertensive drugs. ©2018 Wiley Periodicals, Inc.

  9. [Clinical study of cervical spondylotic radiculopathy treated with massage therapy combined with Magnetic sticking therapy at the auricular points and the cost comparison].

    Science.gov (United States)

    Wang, Saina; Sheng, Feng; Pan, Yunhua; Xu, Feng; Wang, Zhichao; Cheng, Lei

    2015-08-01

    To compare the clinical efficacy on cervical spondylotic radiculopathy between the combined therapy of massage and magnetic-sticking at the auricular points and the simple massage therapy, and conduct the health economics evaluation. Seventy-two patients of cervical spondylotic radiculopathy were randomized into a combined therapy group, and a simple massage group, 36 cases in each one. Finally, 35 cases and 34 cases were met the inclusive criteria in the corresponding groups separately. In the combined therapy group, the massage therapy and the magnetic sticking therapy at auricular points were combined in the treatment. Massage therapy was mainly applied to Fengchi (GB 20), Jianjing (GB 21), Jianwaishu (SI 14), Jianyu (LI 15) and Quchi (LI 11). The main auricular points for magnetic sticking pressure were Jingzhui (AH13), Gan (On12) Shen (CO10), Shenmen (TF4), Pizhixia (AT4). In the simple massage group, the simple massage therapy was given, the massage parts and methods were the same as those in the combined therapy group. The treatment was given once every two days, three times a week, for 4 weeks totally. The cervical spondylosis effect scale and the simplified McGill pain questionnaire were adopted to observe the improvements in the clinical symptoms, clinical examination, daily life movement, superficial muscular pain in the neck and the health economics cost in the patients of the two groups. The effect was evaluated in the two groups. The effective rate and the clinical curative rate in the combined therapy group were better than those in the control group [100. 0% (35/35) vs 85. 3% (29/34), 42. 9% (15/35) vs 17. 6% (6/34), both Pmassage therapy, the massage therapy combined with magnetic sticking therapy at auricular points achieves the better effect and lower cost in health economics.

  10. Combination Therapy Strategies Against Multiple-Resistant Streptococcus Suis

    Directory of Open Access Journals (Sweden)

    Yang Yu

    2018-05-01

    Full Text Available Streptococcus suis is a major swine pathogen, an emerging zoonotic agent responsible for meningitis, endocarditis and septicaemia followed by deafness in humans. The development of antimicrobial resistance in S. suis increases the risk for therapeutic failure in both animals and humans. In this study, we report the synergism of combination therapy against multi-resistant S. suis isolates from swine. Twelve antibiotic profiles were determined against 11 S. suis strains. To investigate their synergistic/antagonistic activity, checkerboard assay was performed for all the possible combinations. In-vitro killing curves and in-vivo treatment trials were used to confirm the synergistic activity of special combinations against S. suis dominant clones. In this study, 11 S. suis isolates were highly resistant to erythromycin, clindamycin, trimethoprim/sulfamethoxazole, and tetracycline with ratios of 80–100%, and the resistance percentages to enrofloxacin, florfenicol, and spectinomycin were ~50%. The checkerboard data identified two combination regimens, ampicillin plus apramycin and tiamulin plus spectinomycin which gave the greatest level of synergism against the S. suis strains. In-vitro kill-curves showed a bacterial reduction of over 3-logCFU with the use of combination treatments, whilst the application of mono-therapies achieve less than a 2-logCFU cell killing. In-vivo models confirm that administration of these two combinations significantly reduced the number of bacterial cells after 24 h of treatment. In conclusions, the combinations of ampicillin plus apramycin and tiamulin plus spectinomycin showed the greatest synergism and may be potential strategies for treatment of multi-resistant S. suis in animal.

  11. Combined tumor therapy

    International Nuclear Information System (INIS)

    Wrba, H.

    1990-01-01

    This comprehensive survey of current methods and achievements first takes a look at the two basic therapies, devoting a chapter each to the surgery and radiotherapy of tumors. The principal subjects of the book, however, are the systemic, adjuvant therapy, biological therapies, hyperthermia and various other therapies (as e.g. treatment with ozone, oxygen, or homeopathic means), and psychotherapy. (MG) With 54 figs., 86 tabs [de

  12. Effectiveness of cognitive behavioral therapy integrated with systematic desensitization, cognitive behavioral therapy combined with eye movement desensitization and reprocessing therapy, and cognitive behavioral therapy combined with virtual reality exposure therapy methods in the treatment of flight anxiety: a randomized trial.

    Science.gov (United States)

    Triscari, Maria Teresa; Faraci, Palmira; Catalisano, Dario; D'Angelo, Valerio; Urso, Viviana

    2015-01-01

    The purpose of the research was to compare the effectiveness of the following treatment methods for fear of flying: cognitive behavioral therapy (CBT) integrated with systematic desensitization, CBT combined with eye movement desensitization and reprocessing therapy, and CBT combined with virtual reality exposure therapy. Overall, our findings have proven the efficacy of all interventions in reducing fear of flying in a pre- to post-treatment comparison. All groups showed a decrease in flight anxiety, suggesting the efficiency of all three treatments in reducing self-report measures of fear of flying. In particular, our results indicated significant improvements for the treated patients using all the treatment programs, as shown not only by test scores but also by participation in the post-treatment flight. Nevertheless, outcome measures maintained a significant effect at a 1-year follow-up. In conclusion, combining CBT with both the application of eye movement desensitization and reprocessing treatment and the virtual stimuli used to expose patients with aerophobia seemed as efficient as traditional cognitive behavioral treatments integrated with systematic desensitization.

  13. Atypical and Typical Winter Depressive Symptoms and Responsiveness to Light Therapy, Cognitive-Behavioral Therapy, or Combination Treatment

    National Research Council Canada - National Science Library

    Johnson, Leigh G; Rohan, Kelly J

    2005-01-01

    ...), group cognitive-behavioral therapy (CBT), or combination therapy (CBT+LT). Atypical and typical symptoms were assessed using subscales of the Structured Interview Guide for the Hamilton Rating Scale for Depression - SAD Version (SIGH-SAD...

  14. The presence of non-organ-specific autoantibodies is associated with a negative response to combination therapy with interferon and ribavirin for chronic hepatitis C

    Directory of Open Access Journals (Sweden)

    Matern Siegfried

    2004-02-01

    Full Text Available Abstract Background Non-organ-specific autoantibodies are found in a considerable number of anti-HCV positive patients. Previous studies investigated the clinical relevance of these antibodies in patients treated with interferon monotherapy, but not combination therapies. Methods Anti-nuclear, anti-smooth muscle, anti-mitochondrial, anti-neutrophil-cytoplasmatic and anti-liver/kidney microsomal antibodies were determined in 78 consecutive anti-HCV positive patients by indirect immunofluorescence. The presence of these antibodies was related to demographic variables and to the outcome of antiviral combination therapy with interferon-α and ribavirin in 65 patients. Results In our study, positivity for autoantibodies was associated with higher alanine aminotransferase levels and higher mean values for HCV-RNA (p Conclusions The absence of non-organ-specific autoantibodies might indicate a significantly higher chance for viral clearance in response to combination therapy for chronic hepatitis C infection. Therefore, despite of an overall higher treatment response, the addition of the immunomodulatory drug ribavirin could accentuate immunological differences that affect treatment outcome and might have been less obvious in earlier studies analysing interferon monotherapy.

  15. Are routine tuberculosis programme data suitable to report on antiretroviral therapy use of HIV-infected tuberculosis patients?

    NARCIS (Netherlands)

    Brouwer, Miranda; Gudo, Paula Samo; Simbe, Chalice Mage; Perdigão, Paula; van Leth, Frank

    2013-01-01

    Antiretroviral therapy (ART) is lifesaving for HIV-infected tuberculosis (TB) patients. ART-use by these patients lag behind compared to HIV-testing and co-trimoxazole preventive therapy. TB programmes provide the data on ART-use by HIV-infected TB patients, however often the HIV services provide

  16. Two patterns of cerebral metabolite abnormalities are detected on proton magnetic resonance spectroscopy in HIV-infected subjects commencing antiretroviral therapy

    International Nuclear Information System (INIS)

    Winston, Alan; Taylor-Robinson, Simon D.; Duncombe, Chris; Li, Patrick C.K.; Gill, John M.; Kerr, Stephen J.; Puls, Rebekah L.; Emery, Sean; Cooper, David A.

    2012-01-01

    Cerebral function impairment remains problematic in subjects with chronic human immunodeficiency virus (HIV) infection despite effective combination antiretroviral therapy (cART). Using cerebral proton magnetic resonance spectroscopy ( 1 H MRS), we aimed to determine if abnormalities could be detected in neurologically asymptomatic HIV-infected subjects electively commencing cART. Therapy-naive, HIV-infected individuals and HIV-uninfected controls underwent 1 H MRS in several anatomical voxels including the mid-frontal grey matter (FGM) and right basal ganglia (RBG). Differences in cerebral metabolite ratios between groups and correlations between immune and virological status were assessed. Forty-six subjects were recruited (26 HIV-infected and 20 control subjects). In the HIV-infected group, mean CD4+ count (SD, cells per microlitre) and plasma HIV RNA (SD, log10 copies per millilitre) were 192 (86) and 4.71 (0.64), respectively. Choline (Cho)/Creatine (Cr) and myoinositol (MI)/Cr ratios were significantly lower in the FGM in HIV-infected subjects compared to controls (0.67 (0.14) versus 0.88 (0.49), p = 0.036, and 0.94 (0.28) and 1.17 (0.26), p = 0.008, for Cho/Cr and MI/Cr, respectively) and Cho/Cr ratio associated with CD4+ lymphocyte count (p = 0.041). N-Acetyl-aspartate (NAA)/Cho ratio was significantly lower in the RBG in HIV-infected subjects compared to controls (2.27 (0.54) versus 2.63 (0.68), p = 0.002), and this was associated with greater plasma HIV RNA load (p = 0.014). Two patterns of cerebral metabolite abnormalities were observed in HIV-infected subjects electively commencing cART. Greater inflammatory metabolite ratios (Cho/Cr and MI/Cr) associated with lower markers of peripheral immune markers (CD4+ lymphocyte count) in the FGM and lower neuronal metabolite ratios (NAA/Cho) associated with greater HIV viraemia in the RBG were present in HIV-infected subjects. (orig.)

  17. Fixed-dose combination therapy for the prevention of cardiovascular disease

    Science.gov (United States)

    de Cates, Angharad N; Farr, Matthew RB; Rees, Karen; Casas, Juan P; Huffman, Mark

    2014-01-01

    This is the protocol for a review and there is no abstract. The objectives are as follows: To determine the effectiveness of fixed-dose combination therapy on optimising CVD risk factors and reducing CVD fatal and non-fatal events for both primary and secondary prevention of CVD. Details of CVD events and risk factors included are listed in the methods. We will also determine any adverse events associated with taking fixed-dose combination therapy. This will include studies conducted in both developed and developing regions of the world. PMID:25267903

  18. Towards antiviral therapies for treating dengue virus infections.

    Science.gov (United States)

    Kaptein, Suzanne Jf; Neyts, Johan

    2016-10-01

    Dengue virus is an emerging human pathogen that poses a huge public health burden by infecting annually about 390 million individuals of which a quarter report with clinical manifestations. Although progress has been made in understanding dengue pathogenesis, a licensed vaccine or antiviral therapy against this virus is still lacking. Treatment of patients is confined to symptomatic alleviation and supportive care. The development of dengue therapeutics thus remains of utmost importance. This review focuses on the few molecules that were evaluated in dengue virus-infected patients: balapiravir, chloroquine, lovastatin, prednisolone and celgosivir. The lessons learned from these clinical trials can be very helpful for the design of future trials for the next generation of dengue virus inhibitors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Safety and Efficacy of Nucleic Acid Polymers in Monotherapy and Combined with Immunotherapy in Treatment-Naive Bangladeshi Patients with HBeAg+ Chronic Hepatitis B Infection.

    Directory of Open Access Journals (Sweden)

    Mamun Al-Mahtab

    Full Text Available Previous in vivo studies have suggested that nucleic acid polymers (NAPs may reduce circulating levels of HBsAg in the blood by blocking its release from infected hepatocytes and that this effect may have clinical benefit. NAP treatment, was evaluated in two clinical studies in patients with HBeAg positive chronic HBV infection. The REP 101 study examined REP 2055 monotherapy in 8 patients and the REP 102 study examined REP 2139-Ca, in monotherapy in 12 patients, 9 of which transitioned to short term combined treatment with pegylated interferon alpha 2a or thymosin alpha 1. In both studies NAP monotherapy was accompanied by 2-7 log reductions of serum HBsAg, 3-9 log reductions in serum HBV DNA and the appearance of serum anti-HBsAg antibodies (10-1712 mIU / ml. Eight of the 9 patients transitioning to combined treatment with immunotherapy (pegylated interferon or thymosin alpha 1 in the REP 102 study experienced HBsAg loss and all 9 patients experienced substantial increases in serum anti-HBsAg antibody titers before withdrawal of therapy. For 52 weeks after removal of REP 2055 therapy, rebound of serum viremia (HBV DNA > 1000 copies / ml, HBsAg > 1IU / ml was not observed in 3 / 8 patients. Suppression of serum virema was further maintained for 290 and 231 weeks in 2 of these patients. After withdrawal of all therapy in the 9 patients that transitioned to combination therapy in the REP 102 study, 8 patients achieved HBV DNA < 116 copies / ml after treatment withdrawal. Viral rebound occurred over a period of 12 to 123 weeks in 7 patients but was still absent in two patients at 135 and 137 weeks of follow-up. Administration tolerability issues observed with REP 2055 were rare with REP 2139-Ca but REP 2139-Ca therapy was accompanied by hair loss, dysphagia and dysgeusia which were considered related to heavy metal exposure endemic at the trial site. These preliminary studies suggest that NAP can elicit important antiviral responses during

  20. Safety and Efficacy of Nucleic Acid Polymers in Monotherapy and Combined with Immunotherapy in Treatment-Naive Bangladeshi Patients with HBeAg+ Chronic Hepatitis B Infection.

    Science.gov (United States)

    Al-Mahtab, Mamun; Bazinet, Michel; Vaillant, Andrew

    2016-01-01

    Previous in vivo studies have suggested that nucleic acid polymers (NAPs) may reduce circulating levels of HBsAg in the blood by blocking its release from infected hepatocytes and that this effect may have clinical benefit. NAP treatment, was evaluated in two clinical studies in patients with HBeAg positive chronic HBV infection. The REP 101 study examined REP 2055 monotherapy in 8 patients and the REP 102 study examined REP 2139-Ca, in monotherapy in 12 patients, 9 of which transitioned to short term combined treatment with pegylated interferon alpha 2a or thymosin alpha 1. In both studies NAP monotherapy was accompanied by 2-7 log reductions of serum HBsAg, 3-9 log reductions in serum HBV DNA and the appearance of serum anti-HBsAg antibodies (10-1712 mIU / ml). Eight of the 9 patients transitioning to combined treatment with immunotherapy (pegylated interferon or thymosin alpha 1) in the REP 102 study experienced HBsAg loss and all 9 patients experienced substantial increases in serum anti-HBsAg antibody titers before withdrawal of therapy. For 52 weeks after removal of REP 2055 therapy, rebound of serum viremia (HBV DNA > 1000 copies / ml, HBsAg > 1IU / ml) was not observed in 3 / 8 patients. Suppression of serum virema was further maintained for 290 and 231 weeks in 2 of these patients. After withdrawal of all therapy in the 9 patients that transitioned to combination therapy in the REP 102 study, 8 patients achieved HBV DNA < 116 copies / ml after treatment withdrawal. Viral rebound occurred over a period of 12 to 123 weeks in 7 patients but was still absent in two patients at 135 and 137 weeks of follow-up. Administration tolerability issues observed with REP 2055 were rare with REP 2139-Ca but REP 2139-Ca therapy was accompanied by hair loss, dysphagia and dysgeusia which were considered related to heavy metal exposure endemic at the trial site. These preliminary studies suggest that NAP can elicit important antiviral responses during treatment which may

  1. Research advances in traditional Chinese medicine combined with interventional therapy for hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    LIU Yang

    2015-01-01

    Full Text Available Interventional therapy has become the first choice of non-surgical treatment for hepatocellular carcinoma (HCC due to its advantages such as little trauma and marked local effect. However, the clinical efficiency is less than expected. One of the possibilities is the resistance of cancer cells to anti-cancer drugs. Increasing attention has been paid to the combination of traditional Chinese medicine (TCM and interventional therapy in HCC treatment. This paper reviews the progress in TCM combined with interventional therapy for HCC at animal experiment and clinical study levels in recent ten years. It is pointed out that the combination therapy with TCM and intervention for HCC has a unique advantage.

  2. Initial paclitaxel improves outcome compared with CMFP combination chemotherapy as front-line therapy in untreated metastatic breast cancer.

    Science.gov (United States)

    Bishop, J F; Dewar, J; Toner, G C; Smith, J; Tattersall, M H; Olver, I N; Ackland, S; Kennedy, I; Goldstein, D; Gurney, H; Walpole, E; Levi, J; Stephenson, J; Canetta, R

    1999-08-01

    To determine the place of single-agent paclitaxel compared with nonanthracycline combination chemotherapy as front-line therapy in metastatic breast cancer. Patients with previously untreated metastatic breast cancer were randomized to receive either paclitaxel 200 mg/m(2) intravenously (IV) over 3 hours for eight cycles (24 weeks) or standard cyclophosphamide 100 mg/m(2)/d orally on days 1 to 14, methotrexate 40 mg/m(2) IV on days 1 and 8, fluorouracil 600 mg/m(2) IV on days 1 and 8, and prednisone 40 mg/m(2)/d orally on days 1 to 14 (CMFP) for six cycles (24 weeks) with epirubicin recommended as second-line therapy. A total of 209 eligible patients were randomized with a median survival duration of 17.3 months for paclitaxel and 13.9 months for CMFP. Multivariate analysis showed that patients who received paclitaxel survived significantly longer than those who received CMFP (P =.025). Paclitaxel produced significantly less severe leukopenia, thrombocytopenia, mucositis, documented infections (all P = .07). Initial paclitaxel was associated with significantly less myelosuppression and fewer infections, with longer survival and similar quality of life and control of metastatic breast cancer compared with CMFP.

  3. Orthodontics-surgical combination therapy for Class III skeletal malocclusion

    Directory of Open Access Journals (Sweden)

    M S Ravi

    2012-01-01

    Full Text Available The correction of skeletal Class III malocclusion with severe mandibular prognathism in an adult individual requires surgical and Othodontic combination therapy. The inter disciplinary approach is the treatment of choice in most of the skeletal malocclusions. A case report of an adult individual with Class III malocclusion, having mandibular excess in sagittal and vertical plane and treated with orthodontics,, bilateral sagittal split osteotomy and Le - Forte I osteotomy for the correction of skeletal, dental and soft tissue discrepancies is herewith presented. The surgical-orthodontic combination therapy has resulted in near-normal skeletal, dental and soft tissue relationship, with marked improvement in the facial esthetics in turn, has helped the patient to improve the self-confidence level.

  4. HIV and antiretroviral therapy: lipid abnormalities and associated cardiovascular risk in HIV-infected patients.

    Science.gov (United States)

    Kotler, Donald P

    2008-09-01

    It has been demonstrated that patients on highly active antiretroviral therapy are at increased risk for developing metabolic abnormalities that include elevated levels of serum triglycerides and low-density lipoprotein cholesterol and reduced levels of high-density lipoprotein cholesterol. This dyslipidemia is similar to that seen in the metabolic syndrome, raising the concern that highly active antiretroviral therapy also potentially increases the risk for cardiovascular complications. This paper reviews the contribution of both HIV infection and the different components of highly active antiretroviral therapy to dyslipidemia and the role of these abnormalities toward increasing the risk of cardiovascular disease in HIV-infected patients; therapeutic strategies to manage these risks are also considered.

  5. Effect of photodynamic therapy (PDT) on Enterococcus faecalis biofilm in experimental primary and secondary endodontic infections.

    Science.gov (United States)

    Tennert, Christian; Feldmann, Katharina; Haamann, Edwina; Al-Ahmad, Ali; Follo, Marie; Wrbas, Karl-Thomas; Hellwig, Elmar; Altenburger, Markus J

    2014-11-04

    To determine the antibacterial effect of photodynamic Therapy on Enterococcus faecalis (E. faecalis) biofilms in experimentally infected human root canals in primary infections and endodontic retreatments. One hundred and sixty single-rooted extracted teeth with one root canal were prepared using ProTaper instruments. Seventy specimens were left without root canal filling and autoclaved. The root canals of another 70 specimens were filled with Thermafil and AH Plus and the root canal fillings were removed after 24 hours using ProTaper D files and plasma sterilized. The specimens were infected with a clinical isolate of E. faecalis for 72 hours. Samples were taken using sterile paper points to determine the presence of E. faecalis in the root canals. The specimens were randomly divided into groups according to their treatment with 20 teeth each and a control. In the PDT group the teeth were treated using PDT, consisting of the photosensitizer toluidine blue and the PDT light source at 635 nm. In the NaOCl (sodium hypochlorite) group the root canals were rinsed with 10 mL of 3% NaOCl. In the NaOCl-PDT group the root canals were rinsed with 10 mL of 3% of sodium hypochlorite and then treated with PDT. Samples were taken after treatments using sterile paper points. Additionally, remaining root canal filling material was recovered from the root canal walls. Survival fractions of the samples were calculated by counting colony-forming units. A one-way analysis of variance (ANOVA) was applied to the data to assess the effect of different treatment techniques. Antimicrobial treatment of root canals caused a significant reduction of bacterial load in all groups. NaOCl irrigation eliminated E. faecalis most effectively. PDT alone was less effective compared to NaOCl irrigation and the combination of NaOCl irrigation and PDT. CFU levels recovered from the filling material after NaOCl irrigation of the root canals were 10fold higher compared to PDT and the combination of Na

  6. Analysis of the factors motivating HCV-infected patients to accept interferon therapy

    Directory of Open Access Journals (Sweden)

    Nagao Yumiko

    2012-08-01

    Full Text Available Abstract Background The aims of this study were to analyze factors motivating the acceptance of interferon (IFN therapy and to clarify the prevalence of oral mucosal diseases in hepatitis C virus (HCV-infected Japanese patients treated with IFN. Findings A total of 94 HCV-infected patients who were admitted to our hospital for IFN therapy were asked questions regarding their motivation to accept IFN therapy and were investigated for the presence of oral lichen planus (OLP before and during IFN treatment. Recommendation and encouragement from other people were the most common factors motivating the acceptance of IFN therapy (49/94, 52.13%. The other motivators were independent decision (30.85%, economic reasons (5.32%, and others. According to multivariate analysis, three factors – sex (male, retreatment after previous IFN therapy, and independent decision to accept IFN therapy - were associated with patients after curative treatment of hepatocellular carcinoma (HCC. The adjusted odds ratios for these three factors were 26.06, 14.17, and 8.72, respectively. The most common oral mucosal lesions included OLP in 11 cases (11.70%. One patient with OLP had postoperative squamous cell carcinoma of the tongue. The rate of sustained virological response (SVR was 45.45% in cases with OLP and 54.55% in cases without OLP. There were no patients who discontinued IFN therapy because of side effects such as oral mucosal diseases. Conclusions We should give full explanation and recommend a course of treatment for a patient to accept IFN therapy. The system to support liver disease as well as oral diseases is also necessary for patient treated for IFN therapy.

  7. Helicobacter pylori and non-steroidal anti-inflammatory drugs: does infection affect the outcome of NSAID therapy?

    Science.gov (United States)

    McCarthy, D. M.

    1998-01-01

    1. H. pylori gastritis appears to increase the likelihood of developing dyspeptic symptoms on NSAID therapy. 2. There is preliminary evidence that the histologic severity of H. pylori gastritis may be adversely affected by NSAID therapy, with a consequent increase in the risk of developing a peptic ulcer, possibly with complications. Whether this results from an effect on the inflammatory process or results from a quantitative increase in H. pylori colonization is unknown. In these respects, ASA may differ from other NSAIDs. 3. Ulcers are more likely to develop during the course of NSAID therapy in those infected with H. pylori; eradication of the infection reduces ulcer recurrence in the face of continued NSAID therapy, and it seems likely that this must reduce but not abolish the risk of GI bleeding in those using NSAIDs. Eradication also reduces the damage (and possibly risks) of low-dose aspirin therapy. 4. While H. pylori and NSAID use are independent risk factors for GI bleeding, whether or not they are interactive remains unresolved. 5. The effect of H. pylori infection on the risk of perforation during NSAID therapy, or conversely, the contribution of NSAID therapy to the risk of perforation in H. pylori-infected subjects, is also unclear at the present time. 6. Only large outcome studies of accurately diagnosed patients (with regard to H. pylori gastritis), and with much more specific detail as to the type of NSAID, dose and duration of therapy, employing only well-defined end-points, such as significant hemorrhage, perforation or death, and avoiding all surrogate markers short of these end points can hope to unravel this tangled web. PMID:10378355

  8. Antiviral Combination Approach as a Perspective to Combat Enterovirus Infections.

    Science.gov (United States)

    Galabov, Angel S; Nikolova, Ivanka; Vassileva-Pencheva, Ralitsa; Stoyanova, Adelina

    2015-01-01

    Human enteroviruses distributed worldwide are causative agents of a broad spectrum of diseases with extremely high morbidity, including a series of severe illnesses of the central nervous system, heart, endocrine pancreas, skeleton muscles, etc., as well as the common cold contributing to the development of chronic respiratory diseases, including the chronic obstructive pulmonary disease. The above mentioned diseases along with the significantly high morbidity and mortality in children, as well as in the high-risk populations (immunodeficiencies, neonates) definitely formulate the chemotherapy as the main tool for the control of enterovirus infections. At present, clinically effective antivirals for use in the treatment of enteroviral infection do not exist, in spite of the large amount of work carried out in this field. The main reason for this is the development of drug resistance. We studied the process of development of resistance to the strongest inhibitors of enteroviruses, WIN compounds (VP1 protein hydrophobic pocket blockers), especially in the models in vivo, Coxsackievirus B (CV-B) infections in mice. We introduced the tracing of a panel of phenotypic markers (MIC50 value, plaque shape and size, stability at 50℃, pathogenicity in mice) for characterization of the drug-mutants (resistant and dependent) as a very important stage in the study of enterovirus inhibitors. Moreover, as a result of VP1 RNA sequence analysis performed on the model of disoxaril mutants of CVB1, we determined the molecular basis of the drug-resistance. The monotherapy courses were the only approach used till now. For the first time in the research for anti-enterovirus antivirals our team introduced the testing of combination effect of the selective inhibitors of enterovirus replication with different mode of action. This study resulted in the selection of a number of very effective in vitro double combinations with synergistic effect and a broad spectrum of sensitive

  9. Successful Treatment of Cutaneous Botryomycosis with a Combination of Minocycline and Topical Heat Therapy

    Directory of Open Access Journals (Sweden)

    Masaya Ishibashi

    2012-05-01

    Full Text Available Cutaneous botryomycosis is a chronic focal infection characterized by a granulomatous inflammatory response to bacterial pathogens such as Staphylococcus aureus. Treatment requires antibiotic therapy and may also require surgical debridement. We employed topical heat therapy and oral minocycline. The lesions became flattened and pigmented after 1 month. We consider that this simple treatment can be an effective and harmless complementary therapy for cutaneous botryomycosis.

  10. ECONOMIC EVALUATION OF COMBINED THERAPY OF ARTERIAL HYPERTENSION BY MARKOV’S MODELING

    Directory of Open Access Journals (Sweden)

    N. S. Maksimchuk-Kolobova

    2015-09-01

    Full Text Available Aim. To evaluate the economic effectiveness of the combined two-drug antihypertensive therapy in patients with arterial hypertension (HT and high cardiovascular risk by Markov’s modeling.Material and methods. Patients (n= 65; 19 males and 46 females with essential HT accompanied by metabolic disorders, history of previous ineffective antihypertensive therapy were included into the study. Patients were randomized into 2 groups. Group V/A was treated with valsartan and amlodipine in fixed-dose combinations of 160/5 and 160/10 mg depending on blood pressure (BP level. Patients of group L/A were treated with losartan 100 mg and amlodipine 5 or 10 mg daily. Treatment duration was 24 weeks. Changes in BP level, and left ventricular hypertrophy (LVH regression were assessed. Economic evaluation was performed on the basis of modeling with specialized software Decision Tree 4.xla.Results. Effect of the two variants of combination therapy on LVH was used to estimate treatment effectiveness and to build the model. Patients were distributed according to the left ventricular mass (LVM at baseline and after 24 weeks of therapy. Significant decrease in LVM was observed in V/A group: from 225.1±71.7 to 186.3±44.5 g (p<0.05. There was no LVM dynamics in L/A group. The model took into account economic and frequency factors for 10 years forecast. V/A therapy is able to prevent 94 deaths, 22 strokes, and 64 myocardial infarction per 1000 patients. Absence of need in treatment of these prevented events can save about 5.5 million RUR for every 1000 patients. It would reduce the total costs per patient during 10 years. V/A therapy is able to save maximal number of quality adjusted life years (QALY due to LVM regression (5.016 years. L/A combination is the most economical variant of pharmacotherapy due to low cost of treatment (16.491.25 RUR per 1 QALY. It would take 286.698.7 RUR additionally for one additional QALY in the treatment with V/A, and it is

  11. Failure of combination therapy with imidocarb dipropionate and toltrazuril to clear Hepatozoon canis infection in dogs.

    Science.gov (United States)

    Pasa, Serdar; Voyvoda, Huseyin; Karagenc, Tulin; Atasoy, Abidin; Gazyagci, Serkal

    2011-09-01

    Current treatments with imidocarb dipropionate for infected dogs with Hepatozoon canis do not always provide parasitological cure. The objective of this study is to determine whether concomitant use of toltrazuril may potentiate the effect of imidocarb dipropionate in the management of H. canis infection (HCI). Twelve dogs were determined to have naturally HCI based on clinical signs, identification of the parasite in blood smears, and serologic assay. The animals were allocated randomly to one of two groups (n = 6 in each group). Dogs in Imi group were given imidocarb dipropionate at a dose of 6 mg/kg body weight subcutaneously in two injections 14 days apart. Imi plus Toltra group was given imidocarb dipropionate as dose mentioned above and toltrazuril at 10 mg/kg/day orally for the first five treatment days. Clinical findings, blood counts and parasitaemia levels in blood before and 14, 28 and 56 days after the initial treatment were performed to evaluate treatment response. The overall clinical efficacy of imidocarb dipropionate with and without toltrazuril was 83.3% and 66.7%, respectively; with a mean recovery time of 21.0 and 25.6 days, respectively. A substantial main effect of time on mean PCV, Hb, WBC, neutrophil and PLT and gradual reduction of parasitaemia were significantly observed in both groups (P < 0.05), whereas no significant difference was noticed between the studied protocols. The parasitologic cure rate at the end of eight weekly observation period was 16.6% and 33.3% in Imi and Imi plus Toltra groups, respectively. Similar clinicopathologic and parasitologic responses were observed in both treated groups; thus, it was concluded that toltrazuril does not reveal additional benefit to imidocarb therapy in dogs with HCI.

  12. Evaluation of the Efficacy of Combined Therapy of Methotrexate and Etanercept versus Methotrexate as a Mono-Therapy.

    Science.gov (United States)

    Rexhepi, Sylejman; Rexhepi, Mjellma; Rexhepi, Blerta; Sahatçiu-Meka, Vjollca; Mahmutaj, Vigan

    2018-05-20

    This study aims to evaluate the efficacy of Methotrexate (MTX) alone and combined therapy with Etanercept (ETN) and Methotrexate in patients with active rheumatoid arthritis (RA). In the randomised control study, conducted in the period from March 2014 until March 2016, we evaluated the efficacy of the treatment of patients with RA with MTX as monotherapy and combination treatment with MTX and ETN. In the Clinic of Rheumatology in Prishtina, 90 adult patients with RA were treated in combination with ETN (doses of 50 mg subcutaneously/weekly), with oral MTX (doses up to 20 mg weekly), and MTX alone (doses up to 20 mg weekly) during this period of two years. Clinical response was assessed using European League against Rheumatism (EULAR)/American College of Rheumatology (ACR) Criteria and the Disease Activity Score (DAS28). Radiographic changes were measured in the beginning and at the end of the study using Larsen's method. Of the cohort groups of 90 patients, mean age of 55.63, 15 patients, (16.6 %) were treated with combined therapy (ETN plus MTX) and 75 patients (83.3%) with monotherapy (MTX). After two years of treatment the group with combined therapy resulted with improvement of acute phase reactants as erythrocyte sedimentation rate (ESR) for the first hour (41.1 vs. 10.3 mm/hour) and C - reactive protein (CRP) (40.8 vs. 6 mg/liter), and compared to the group treated with monotherapy, there were no significant changes (ESR: 45.7 vs 34.3 mm/hour; CRP: 48 vs 24 mg/liter). Before the treatment, the severity of the disease was high, wherein the group with combined therapy DAS28 was 5.32, compared to the monotherapy group whom DAS28 was 5.90. After 2 years of treatment, we had significant changes in the results of DAS28, wherein the group treated with ETN plus MTX DAS28 was 2.12 ± 0.15, while in the group of patients treated with MTX DAS28 were 3.75 ± 0.39 (t = 13.03; df = 58; p < 0.0001). The group with combined therapy showed no evidence of radiographic

  13. Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance.

    Science.gov (United States)

    Khdair, Ayman; Chen, Di; Patil, Yogesh; Ma, Linan; Dou, Q Ping; Shekhar, Malathy P V; Panyam, Jayanth

    2010-01-25

    Tumor drug resistance significantly limits the success of chemotherapy in the clinic. Tumor cells utilize multiple mechanisms to prevent the accumulation of anticancer drugs at their intracellular site of action. In this study, we investigated the anticancer efficacy of doxorubicin in combination with photodynamic therapy using methylene blue in a drug-resistant mouse tumor model. Surfactant-polymer hybrid nanoparticles formulated using an anionic surfactant, Aerosol-OT (AOT), and a naturally occurring polysaccharide polymer, sodium alginate, were used for synchronized delivery of the two drugs. Balb/c mice bearing syngeneic JC tumors (mammary adenocarcinoma) were used as a drug-resistant tumor model. Nanoparticle-mediated combination therapy significantly inhibited tumor growth and improved animal survival. Nanoparticle-mediated combination treatment resulted in enhanced tumor accumulation of both doxorubicin and methylene blue, significant inhibition of tumor cell proliferation, and increased induction of apoptosis. These data suggest that nanoparticle-mediated combination chemotherapy and photodynamic therapy using doxorubicin and methylene blue has significant therapeutic potential against drug-resistant tumors. Copyright 2009 Elsevier B.V. All rights reserved.

  14. IMMUNOPATHOGENESIS OF ACUTE RESPIRATORY INFECTIONS AND TACTICS OF RATIONAL CHOICE OF ETIOTROPIC IMMUNOMODULATORY THERAPIES IN CHILDREN

    Directory of Open Access Journals (Sweden)

    V. V. Malinovskaya

    2013-01-01

    Full Text Available The article demonstrates that the basis for pathogenesis of acute respiratory infection (ARI is a deficiency in a number of factors of virus protection. This deficiency manifests itself through low concentration of interferon and secretory IgA in the nasal mucosa at higher levels of IL-8, alongside with low serum antiviral activity and significant inhibition of interferon production and reduction of the compensatory mechanisms of adaptive immunity. These disorders require prescription of alpha-interferon preparations. For infants and children with a burdened pre-morbid background, regardless of age, such preparations can be administered with all clinical forms of ARI; in older children — with severe forms, including complications. Alpha-interferon preparations can be introduced at in any stage of the disease. Combination therapy with alpha-interferon drugs (VIFERON® suppositories and VIFERON® ointment allows for enhanced clinical and immunological effects of therapy.

  15. Laser therapy in women genital Chlamydia trachomatis infection complicated with PID and infertility

    Science.gov (United States)

    Brinzan, Daniela; Paiusan, Lucian; Smeu, Claudia-Ramona

    2018-04-01

    Genital Chlamydia Trachomatis infection is one of the most common sexually transmitted infections with more than 50 million new cases occurred globally every year. Underdiagnosed and untreated, it can generate long term severe complications including PID, infertility, ectopic pregnancy and chronic pelvic pain. Among 20 patients diagnosed with PID and infertility in our medical office during one year, we selected a study group of 10 patients with genital Chlamydia Trachomatis infection. The diagnostic methods used were anamnesis, clinical examination, Pap smear, bacteriological and serological tests, ultra sound examination. The group of patients selected was monitored for one year. The treatment took into account general measures for both partners and specific measures (antibiotic treatment and focused laser therapy). The initial group was split in two, group A treated only with antibiotics and group B treated with both antibiotics and laser therapy. All the 5 patients of group B presented an improvement of the clinical manifestations and 3 of them ended up with pregnancy. On the other hand, in group B, only one patient manifested total disappearance of pains and the infertility persisted for all. It is noteworthy that the association of laser therapy in the treatment of Chlamydia Trachomatis infection has brought significant improvement in the inflammatory processes of internal genitalia (PID) and in the fertility of the couple.

  16. Antimicrobial photodynamic therapy in a mouse model of Acinetobacter baumannii burn infection

    Science.gov (United States)

    Dai, Tianhong; Tegos, George P.; Lu, Zongshun; Zhiyentayev, Timur; Huang, Liyi; Franklin, Michael J.; Baer, David G.; Hamblin, Michael R.

    2009-06-01

    Multi-drug resistant Acinetobacter baumanii infections represent a growing problem, especially in traumatic wounds and burns suffered by military personnel injured in Middle Eastern conflicts. Effective treatment using traditional antibiotics can be extremely difficult and new antimicrobial approaches are being investigated. One of these antimicrobial alternatives could be the combination of non-toxic photosensitizers (PS) and visible light known as photodynamic therapy (PDT). We report on the establishment of a new mouse model of full thickness thermal burns infected with a bioluminescent derivative of a clinical Iraqi isolate of A. baumannii and its PDT treatment by topical application of a PS produced by covalent conjugation chlorin(e6) to polyethylenimine followed by illumination of the burn surface with red light. Application of 108 A. baumannii cells to the surface of 10-second burns made on the dorsal surface of shaved female BALB/c mice led to chronic infections that lasted on average 22 days characterized by a remarkably stable bacterial bioluminescence. PDT carried out on day 0 soon after applying bacteria gave over three logs of loss of bacterial luminescence in a light exposure dependent manner, while PDT carried out on day 1 and day 2 gave approximately a 1.7-log reduction. Application of PS dissolved in 10% or 20% DMSO without light gave only modest reduction in bacterial luminescence from mouse burns. Some bacterial regrowth in the treated burn was observed but was generally modest. It was also found that PDT did not lead to inhibition of wound healing. The data suggest that PDT may be an effective new treatment for multi-drug resistant localized A. baumannii infections.

  17. A Systematic Review of Antiretroviral Adherence Interventions for HIV-Infected People Who Use Drugs

    OpenAIRE

    CampBinford, Meredith; Kahana, Shoshana Y.; Altice, Frederick L.

    2012-01-01

    HIV-infected persons who use drugs (PWUDs) are particularly vulnerable for suboptimal combination antiretroviral therapy (cART) adherence. A systematic review of interventions to improve cART adherence and virologic outcomes among HIV-infected PWUDs was conducted. Among the 45 eligible studies, randomized controlled trials suggested directly administered antiretroviral therapy, medication-assisted therapy (MAT), contingency management, and multi-component, nurse-delivered interventions provid...

  18. Combination therapy in a patient with chronic neuronopathic Gaucher disease: a case report.

    Science.gov (United States)

    Ceravolo, Ferdinando; Grisolia, Michele; Sestito, Simona; Falvo, Francesca; Moricca, Maria Teresa; Concolino, Daniela

    2017-01-20

    The variants of neuronopathic Gaucher disease may be viewed as a clinical phenotypic continuum divided into acute and chronic forms. The chronic neuronopathic form of Gaucher disease is characterized by a later onset of neurological symptoms and protracted neurological and visceral involvement. The first-choice treatment for nonneuronopathic Gaucher disease is enzyme replacement therapy with recombinant analogues of the deficient human enzyme glucocerebrosidase. Enzyme replacement therapy has been shown to improve hematological and bone manifestations associated with Gaucher disease, but, as with most proteins, recombinant enzymes cannot cross the blood-brain barrier, which prevents effects on neurological manifestations. Substrate reduction therapy with miglustat (N-butyldeoxynojirimycin) inhibits glucosylceramide synthase, which catalyzes the first step in glycosphingolipid synthesis. Because miglustat can cross the blood-brain barrier, it has been suggested that, combined with enzyme replacement therapy, it might be effective in treating neurological symptoms in patients with neuronopathic Gaucher disease. We report observed effects of combined enzyme replacement therapy and substrate reduction therapy in a 7-year-old Caucasian boy with neuronopathic Gaucher disease who was homozygous for L444P mutations. He had received enzyme replacement therapy from the age of 18 months, and concomitant miglustat treatment was commenced, with dosing according to body surface area uptitrated over 1 month with dietary modifications when he reached the age of 30 months. He experienced mild diarrhea after commencing miglustat therapy, which decreased in frequency/severity over time. His splenomegaly was reduced, and his hematological values and plasma angiotensin-converting enzyme activity normalized. Plasma chitotriosidase also showed substantial and sustained decreases. After 5 years of combination therapy, the patient showed no signs of neurological impairment. This case

  19. The advance in the therapy of therapy-resistant keloids

    International Nuclear Information System (INIS)

    Yao Hongxia; Zhang Jinshan

    2009-01-01

    Keloids are huamn benign dermal tumors, excessive fibroproliferative disorders that enlarge and extend beyond the margins of the origin wounds. Some keloids have proven to be very resistant to treatment, for example, several treatment modalities including surgical excision in combination with radiotherapy in the form of roentgen radiation (X-ray), pharmaceuticals, intralesional corticosteroids or calcium ions blocking agents, silicone gel sheets, physical therapy such as pressuretherapy, lasertherapy, cryotherpay might be less efficacious, and sometimes they cannot be performed because of limited conditions. Some keloids have higher recurrence rates. It is difficult to treat some keloids with complications of infection. 32 P-phosphours combination with vittamin E may be iuseful to treat therapy-resistant keloids. (authors)

  20. Frequency of thyroid dysfunctions during interferon alpha treatment of single and combination therapy in hepatitis C virus-infected patients: a systematic review based analysis.

    Directory of Open Access Journals (Sweden)

    Chandrasekharan Nair Kesavachandran

    Full Text Available Thyroid dysfunction is the commonest endocrinopathy associated with HCV infection due to interferon-based treatment. This comprehensive and systematic review presents the available evidence for newly developed thyroid antibodies and dysfunctions during interferon treatment (both single and combination in HCV patients.This systematic review was conducted in accordance with the PRISMA guidelines. The data generated were used to analyze the risk for thyroid dysfunctions during interferon (IFN treatment in HCV patients. There was a wide range in the incidence of newly developed thyroid dysfunctions and thyroid antibodies in HCV patients during IFN treatment (both single and combination. The wide range of incidence also denoted the possibility of factors other than IFN treatment for thyroid-related abnormalities in HCV patients. These other factors include HCV viral factors, genetic predisposition, environmental factors, and patho-physiological factors. Variations in IFN dosage, treatment duration of IFN, definition/criteria followed in each study for thyroid dysfunction and irregular thyroid function testing during treatment in different studies influence the outcome of the single studies and jeopardise the validity of a pooled risk estimate of side effects of thyroid dysfunction. Importantly, reports differ as to whether the thyroid-related side effects disappear totally after withdrawal of the IFN treatment.The present review shows that there is a wide range in the incidence of newly developed thyroid dysfunctions and thyroid antibodies in IFN treated HCV patients. This is a comprehensive attempt to collate relevant data from 56 publications across several nations about IFN (both mono and combination therapy related thyroid dysfunction among HCV patients. The role of each factor in causing thyroid dysfunctions in HCV patients treated with IFN should be analyzed in detail in future studies, for a better understanding of the problem and sounder

  1. Biological basis of combination therapy with radiation and bleomycin

    International Nuclear Information System (INIS)

    Fukuda, Hiroshi; Matsuzawa, Taiju; Yokoyama, Kumiko; Okuyama, Shinichi; Yamaura, Hiroshi

    1976-01-01

    The biological basis for combination therapy with radiation and bleomycin (BLM) was studied on C 2 W cells growing in vitro. When BLM was added to the medium before or after irradiation, a potentiating effect was observed. The potentiation remained for 4-6 hours after irradiation. To make clear the mechanism, both type of repair from radiation damage (Elkind type and PLD) by BLM were examined. BLM didn't inhibit the Elkind type recovery but it did inhibit the repair of potentially lethal damage (PLD repair). Plateau phase C 2 W cells were irradiated, incubated at 37 0 C for a various number of hours, then trypsinized for colony formation. PLD repair was inhibited when BLM was added immediately after irradiation. Based on such experimental results, we treated lung cancer with combination of radiation and BLM. BLM was injected intravenously within 30 minutes after irradiation. Although it seems too early to discuss the result of the combination therapy, it is very promising. (J.P.N.)

  2. Biological basis of combination therapy with radiation and bleomycin

    Energy Technology Data Exchange (ETDEWEB)

    Fukuda, H; Matsuzawa, T; Yokoyama, K; Okuyama, S; Yamaura, H [Tohoku Univ., Sendai (Japan). Research Inst. for Tuberculosis, Leprosy and Cancer

    1976-01-01

    The biological basis for combination therapy with radiation and bleomycin (BLM) was studied on C/sub 2/W cells growing in vitro. When BLM was added to the medium before or after irradiation, a potentiating effect was observed. The potentiation remained for 4-6 hours after irradiation. To make clear the mechanism, both type of repair from radiation damage (Elkind type and PLD) by BLM were examined. BLM didn't inhibit the Elkind type recovery but it did inhibit the repair of potentially lethal damage (PLD repair). Plateau phase C/sub 2/W cells were irradiated, incubated at 37/sup 0/C for a various number of hours, then trypsinized for colony formation. PLD repair was inhibited when BLM was added immediately after irradiation. Based on such experimental results, we treated lung cancer with combination of radiation and BLM. BLM was injected intravenously within 30 minutes after irradiation. Although it seems too early to discuss the result of the combination therapy, it is very promising.

  3. Congenital Cytomegalovirus Infection: New Prospects for Prevention and Therapy

    Science.gov (United States)

    Swanson, Elizabeth C.; Schleiss, Mark R.

    2013-01-01

    SYNOPSIS Cytomegalovirus (CMV) is the most common congenital viral infection in the developed world, with an overall birth prevalence of approximately 0.6%. Approximately 10% of congenitally infected infants have signs and symptoms of disease at birth, and these symptomatic infants have a high risk for demonstration of subsequent neurologic sequelae, including sensorineural hearing loss (SNHL), mental retardation, microcephaly, development delay, seizure disorders, and cerebral palsy. Antiviral therapy of children with symptomatic central nervous system (CNS) congenital CMV infection is effective at reducing the risk of long-term disabilities and should be offered to families with affected newborns. An effective pre-conceptual vaccine against CMV could, by preventing congenital infection, protect against long-term neurological sequelae and other disabilities. A variety of active and passive immunization strategies are in clinical trials and are likely to be licensed in the next few years. Until a vaccine is licensed, preventive strategies aimed at reducing transmission should be emphasized and public awareness increased, particularly among women of child-bearing age. PMID:23481104

  4. Effect of antimicrobial therapy on bowel flora and bacterial infection in irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Brook, Itzhak; Walker, R.I.; MacVittie, T.J.

    1988-05-01

    Mice exposed to 10 Gy cobalt-60 radiation were given intramuscular antimicrobial therapy of gentamicin, metronidazole, or a combination. Mortality in mice treated with metronidazole alone or in combination with gentamicin occurred earlier than in controls (P < 0.001). Microorganisms were recovered from blood, spleen, and liver of the metronidazole-treated mice earlier than from other groups. Predominant organisms recovered from these animals were Enterobacteriaceae. Quantitative cultures of ileal flora showed decrease in aerobic, facultative anaerobic and strict anaerobic bacteria after irradiation, and a subsequent increase only in the number of strict aerobic bacteria. Compared to untreated mice, a rapid decrease (by 8.8 logs) in anaerobic flora occurred in mice treated with metronidazole 5 days after irradiation, followed by a rapid increase in the number of aerobic organisms which coincided with the earlier mortality in this group. Data suggest that antimicrobial agents decreasing the number of the strict anaerobic component of the gut flora enhance systemic infection by aerobic or facultative anaerobic bacteria, facilitating post-irradiation mortality.

  5. Effect of antimicrobial therapy on bowel flora and bacterial infection in irradiated mice

    International Nuclear Information System (INIS)

    Brook, Itzhak; Walker, R.I.; MacVittie, T.J.

    1988-01-01

    Mice exposed to 10 Gy cobalt-60 radiation were given intramuscular antimicrobial therapy of gentamicin, metronidazole, or a combination. Mortality in mice treated with metronidazole alone or in combination with gentamicin occurred earlier than in controls (P < 0.001). Microorganisms were recovered from blood, spleen, and liver of the metronidazole-treated mice earlier than from other groups. Predominant organisms recovered from these animals were Enterobacteriaceae. Quantitative cultures of ileal flora showed decrease in aerobic, facultative anaerobic and strict anaerobic bacteria after irradiation, and a subsequent increase only in the number of strict aerobic bacteria. Compared to untreated mice, a rapid decrease (by 8.8 logs) in anaerobic flora occurred in mice treated with metronidazole 5 days after irradiation, followed by a rapid increase in the number of aerobic organisms which coincided with the earlier mortality in this group. Data suggest that antimicrobial agents decreasing the number of the strict anaerobic component of the gut flora enhance systemic infection by aerobic or facultative anaerobic bacteria, facilitating post-irradiation mortality. (author)

  6. PREDNISONE THERAPY SAFETY FOR TREATMENT OF PATIENTS WITH MIX OF TUBERCULOSIS AND HIV-INFECTION

    Directory of Open Access Journals (Sweden)

    G. V. Maksimov

    2013-01-01

    Full Text Available Abstract. The study of prednisone safety for treatment of TB mixed with HIV-infection has been conducted. Two groups of patients were compared. The first group was consisted of 88 patients who were treated by prednisone and standard tuberculosis therapy, the second group of patients presented by 45 patients received only tuberculosis medicines. It was demonstrated that in case of prednisone using (1st group the number of CD4 limphocytes increased, intoxication symptoms disappeared fast and recovery process accelerated. Increasing of cases with unfavorable course of TB and HIV-infection in patients of first group was not registered in compare with the second group. Thus, using of prednisone therapy to treat TB mixed with HIV-infection was safe, not lead to unfavorable course of TB or HIV-infection. Such kind of treatment especially important for patients with exudative reactions.

  7. HIV Maintains an Evolving and Dispersed Population in Multiple Tissues during Suppressive Combined Antiretroviral Therapy in Individuals with Cancer.

    Science.gov (United States)

    Rose, Rebecca; Lamers, Susanna L; Nolan, David J; Maidji, Ekaterina; Faria, N R; Pybus, Oliver G; Dollar, James J; Maruniak, Samuel A; McAvoy, Andrew C; Salemi, Marco; Stoddart, Cheryl A; Singer, Elyse J; McGrath, Michael S

    2016-10-15

    While combined antiretroviral therapy (cART) can result in undetectable plasma viral loads, it does not eradicate HIV infection. Furthermore, HIV-infected individuals while on cART remain at an increased risk of developing serious comorbidities, such as cancer, neurological disease, and atherosclerosis, suggesting that during cART, tissue-based HIV may contribute to such pathologies. We obtained DNA and RNA env, nef, and pol sequences using single-genome sequencing from postmortem tissues of three HIV(+) cART-treated (cART(+)) individuals with undetectable viral load and metastatic cancer at death and performed time-scaled Bayesian evolutionary analyses. We used a sensitive in situ hybridization technique to visualize HIV gag-pol mRNA transcripts in cerebellum and lymph node tissues from one patient. Tissue-associated virus evolved at similar rates in cART(+) and cART-naive (cART(-)) patients. Phylogenetic trees were characterized by two distinct features: (i) branching patterns consistent with constant viral evolution and dispersal among tissues and (ii) very recently derived clades containing both DNA and RNA sequences from multiple tissues. Rapid expansion of virus near death corresponded to wide-spread metastasis. HIV RNA(+) cells clustered in cerebellum tissue but were dispersed in lymph node tissue, mirroring the evolutionary patterns observed for that patient. Activated, infiltrating macrophages were associated with HIV RNA. Our data provide evidence that tissues serve as a sanctuary for wild-type HIV during cART and suggest the importance of macrophages as an alternative reservoir and mechanism of virus spread. Combined antiretroviral therapy (cART) reduces plasma HIV to undetectable levels; however, removal of cART results in plasma HIV rebound, thus highlighting its inability to entirely rid the body of infection. Additionally, HIV-infected individuals on cART remain at high risk of serious diseases, which suggests a contribution from residual HIV. In

  8. Disseminated BCG infection in a patient with severe combined immunodeficiency

    International Nuclear Information System (INIS)

    Han, Tae Il; Kim, In One; Kim, Woo Sun; Yeon, Kyung Mo

    2000-01-01

    Disseminated mycobacterial infection after bacillus Calmette-Guerin (BCG) accination is a very rare disorder, occurring mostly in patients with immunologic eficiency. We report a case of disseminated BCG infection in a 16-month-old girl with severe combined immunodeficiency. Plain radiographs showed multiple osteolytic lesions in the femora, tibiae, humerus, and phalanges. Abdominal sonography and CT scanning revealed multiple nodules in the spleen, and portocaval lymphadenopathy

  9. Disseminated BCG infection in a patient with severe combined immunodeficiency

    Energy Technology Data Exchange (ETDEWEB)

    Han, Tae Il [Eulji University School of Medicine, Taejon (Korea, Republic of); Kim, In One; Kim, Woo Sun; Yeon, Kyung Mo [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2000-06-01

    Disseminated mycobacterial infection after bacillus Calmette-Guerin (BCG) accination is a very rare disorder, occurring mostly in patients with immunologic eficiency. We report a case of disseminated BCG infection in a 16-month-old girl with severe combined immunodeficiency. Plain radiographs showed multiple osteolytic lesions in the femora, tibiae, humerus, and phalanges. Abdominal sonography and CT scanning revealed multiple nodules in the spleen, and portocaval lymphadenopathy.

  10. EFFICACY OF PANAVIR® AND ACYCLOVIR IN THE COMPLEX THERAPY OF HERPETIC INFECTION-COMPLICATED RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    O N Egorova

    2009-01-01

    Subjects and methods. One hundred and thirty patients with recurrent herpesvirus infection were enrolled in the prospective comparative study. The patients were divided into 3 groups: 1 in addition to the basic therapy, the patients received Panavir®; 2 those who took Acyclovir; and 3 those who had the basic therapy alone. In 90 of the 130 examinees, high titers of antiviral IgG antibodies to cytomegalovirus and Epstein-Barr virus were found in 60 and 48,8%, respectively. The interferon-deficiency syndrome was diagnosed in 72 (80,0% patients. Results. Virostatic therapy may be recommended for patients with RA concurrent with recurrent herpesvirus infection.

  11. Ethical hot spots of combined individual and group therapy: applying four ethical systems.

    Science.gov (United States)

    Brabender, Virginia M; Fallon, April

    2009-01-01

    Abstract Combined therapy presents ethical quandaries that occur in individual psychotherapy and group psychotherapy, and dilemmas specifically associated with their integration. This paper examines two types of ethical frameworks (a classical principle-based framework and a set of context-based frameworks) for addressing the ethical hot spots of combined therapy: self-referral, transfer of information, and termination. The principle-based approach enables the practitioner to see what core values may be served or violated by different courses of action in combined therapy dilemmas. Yet, the therapist is more likely to do justice to the complexity and richness of the combined therapy situation by supplementing a principle analysis with three additional ethical frameworks. These approaches are: virtue ethics, feminist ethics, and casuistry. An analysis of three vignettes illustrates how these contrasting ethical models not only expand the range of features to which the therapist attends but also the array of solutions the therapist generates.

  12. Early experience of proton beam therapy combined with chemotherapy for locally advanced oropharyngeal cancer

    International Nuclear Information System (INIS)

    Ishikawa, Youjirou; Nakamura, Tatsuya; Takada, Akinori; Takayama, Kanako; Makita, Chiyoko; Suzuki, Motohisa; Azami, Yusuke; Kikuchi, Yasuhiro; Fuwa, Nobukazu

    2013-01-01

    Between 2009 and 2012, 10 patients with advanced oropharyngeal cancer underwent proton therapy combined with chemotherapy. The initial results of this therapy were 8 complete response (CR) and 2 partial response (PR), local recurrence was detected 1 patient. Proton beam therapy combined with chemotherapy is thought to be an effective treatment for locally advanced oropharyngeal cancer. (author)

  13. Probiotic therapy: immunomodulating approach toward urinary tract infection.

    Science.gov (United States)

    Amdekar, Sarika; Singh, Vinod; Singh, Desh Deepak

    2011-11-01

    Urinary tract infection (UTI) is an extremely common health problem, with an unpredictable history. Members of enterobacteriaceae family such as Escherichia coli, which are normal inhabitants of human intestines, account for the majority of these uncomplicated infections. Rarely, UTI can result from virus or fungus. There is a close correlation between loss of the normal genital microbiota, particularly Lactobacillus species, and an increased incidence of genital and bladder infections. Although antimicrobial agents are generally effective in eradicating these infections, there is a high incidence of recurrence. Use of Lactobacillus species to combat UTI is now giving modern concept of modern genitourinary vaccine with the facts that it not only maintains low pH of the genital area, produces hydrogen peroxide and hinders the growth of E. coli but also activates Toll-like receptor-2 (TLR2), which produces interleukin-10 (IL-10) and myeloid differentiation factor 88 (MyD88). E. coli activates TLR4, which is responsible for the activation of IL-12, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). This process downregulates inflammatory reactions caused due to pathogens. Current review covers the probiotics-based TLR therapy and shed some knowledge for the use of Lactobacillus species as probiotics.

  14. Wound infections after median sternotomy treated by VAC therapy, summary of results, and risk factor analysis.

    Science.gov (United States)

    Hulman, M; Bezak, B; Artemiou, P; Cikrai, R

    2017-01-01

    The aim of this study is to summarize results and analyze risk factors for the development of wound infection in heart surgery patients after median sternotomy. In this retrospective analysis with assessment of multiple risk factors, we examined 143 patients with infection after median sternotomy treated with VAC therapy from total of 4,650 patients operated in our department from 2012 to 2015. Total of 143 patients developed significant SSI treated by VAC therapy following cardiac surgery. Of these, only 14 patients developed DSWI and one patient was diagnosed with suspected osteomyelitis. BMI, female gender, and use of BIMA proved to be statistically significant risk factors in our study (p infection (p infection proved to be a significant prognostic factor for patients' outcome (p infection (Tab. 3, Ref. 30).

  15. Adjuvant combined ozone therapy for extensive wound over tibia

    Directory of Open Access Journals (Sweden)

    Prasham Shah

    2011-01-01

    Full Text Available Disinfectant and antibacterial properties of ozone are utilized in the treatment of nonhealing or ischemic wounds. We present here a case of 59 years old woman with compartment syndrome following surgical treatment of stress fracture of proximal tibia with extensively infected wound and exposed tibia to about 4/5 of its extent. The knee joint was also infected with active pus draining from a medial wound. At presentation the patient had already taken treatment for 15 days in the form of repeated wound debridements and parenteral antibiotics, which failed to heal the wound and she was advised amputation. Topical ozone therapy twice daily and ozone autohemotherapy once daily were given to the patient along with daily dressings and parenteral antibiotics. Within 5 days, the wound was healthy enough for spilt thickness skin graft to provide biological dressing to the exposed tibia bone. Topical ozone therapy was continued for further 5 days till the knee wound healed. On the 15th day, implant removal, intramedullary nailing, and latissimus dorsi pedicle flap were performed. Both the bone and the soft tissue healed without further complications and at 20 months follow-up, the patient was walking independently with minimal disability.

  16. Enhanced Prophylaxis plus Antiretroviral Therapy for Advanced HIV Infection in Africa.

    Science.gov (United States)

    Hakim, James; Musiime, Victor; Szubert, Alex J; Mallewa, Jane; Siika, Abraham; Agutu, Clara; Walker, Simon; Pett, Sarah L; Bwakura-Dangarembizi, Mutsa; Lugemwa, Abbas; Kaunda, Symon; Karoney, Mercy; Musoro, Godfrey; Kabahenda, Sheila; Nathoo, Kusum; Maitland, Kathryn; Griffiths, Anna; Thomason, Margaret J; Kityo, Cissy; Mugyenyi, Peter; Prendergast, Andrew J; Walker, A Sarah; Gibb, Diana M

    2017-07-20

    In sub-Saharan Africa, among patients with advanced human immunodeficiency virus (HIV) infection, the rate of death from infection (including tuberculosis and cryptococcus) shortly after the initiation of antiretroviral therapy (ART) is approximately 10%. In this factorial open-label trial conducted in Uganda, Zimbabwe, Malawi, and Kenya, we enrolled HIV-infected adults and children 5 years of age or older who had not received previous ART and were starting ART with a CD4+ count of fewer than 100 cells per cubic millimeter. They underwent simultaneous randomization to receive enhanced antimicrobial prophylaxis or standard prophylaxis, adjunctive raltegravir or no raltegravir, and supplementary food or no supplementary food. Here, we report on the effects of enhanced antimicrobial prophylaxis, which consisted of continuous trimethoprim-sulfamethoxazole plus at least 12 weeks of isoniazid-pyridoxine (coformulated with trimethoprim-sulfamethoxazole in a single fixed-dose combination tablet), 12 weeks of fluconazole, 5 days of azithromycin, and a single dose of albendazole, as compared with standard prophylaxis (trimethoprim-sulfamethoxazole alone). The primary end point was 24-week mortality. A total of 1805 patients (1733 adults and 72 children or adolescents) underwent randomization to receive either enhanced prophylaxis (906 patients) or standard prophylaxis (899 patients) and were followed for 48 weeks (loss to follow-up, 3.1%). The median baseline CD4+ count was 37 cells per cubic millimeter, but 854 patients (47.3%) were asymptomatic or mildly symptomatic. In the Kaplan-Meier analysis at 24 weeks, the rate of death with enhanced prophylaxis was lower than that with standard prophylaxis (80 patients [8.9% vs. 108 [12.2%]; hazard ratio, 0.73; 95% confidence interval [CI], 0.55 to 0.98; P=0.03); 98 patients (11.0%) and 127 (14.4%), respectively, had died by 48 weeks (hazard ratio, 0.76; 95% CI, 0.58 to 0.99; P=0.04). Patients in the enhanced-prophylaxis group had

  17. [Optimization of postoperative medical therapy of infective endocarditis in patients with congenital valvular heart disease].

    Science.gov (United States)

    Chistyakov, I S; Medvedev, A P; Pichugin, V V

    2016-01-01

    The purpose of this study was to evaluate the effectiveness of combined surgical and medical treatment of infective endocarditis in patients with congenital valvular heart disease when included in a regimen of the drug Reamberin. In this regard, the analysis of the effectiveness of a combination regimen of 74 patients with valvular congenital heart diseases complicated with infective endocarditis. Given the indications for surgical correction operative technique features and possible technical difficulties in carrying out such operations, due to the inflammatory changes and tissue destruction, and ways to overcome them. For the correction of metabolic disorders in the postoperative period, 47 patients (main group) was appointed Reamberin: once, intravenous drip 400 ml/day during the first 5 days after surgery. 27 patients (control group) was conducted infusion therapy depending on the severity of the condition according to the classical scheme. In addition to standard clinical and laboratory examination, to assess the effectiveness of Reamberin was investigated catalase activity of CPK in blood serum in the dynamics of observation (1, 3 and 5 days after surgery). It is revealed that surgical approach, used in complex treatment of patients with valvular congenital heart diseases, including reorganization of the cavities of the heart, increasing the frequency of joints and the use of reinforcing strips of synthetic material that prevents the cutting of sutures through the inflamed tissue has achieved good short-and long-term results. Infective endocarditis and destruction of the valvular annulus fibrosus the use of a frame of strips of polytetrafluoroethylene allows you to restore its integrity and to implant a mechanical prosthesis. The inclusion in the regimen of patients with infective endocarditis complicated by cardiac insufficiency in the early postoperative period the drug Reamberin improves the efficiency of treatment by a more rapid restoration of the normal

  18. Resolution of disseminated fusariosis in a child with acute leukemia treated with combined antifungal therapy: a case report

    Directory of Open Access Journals (Sweden)

    Zarallo Luis

    2007-05-01

    Full Text Available Abstract Background Fusarium spp. is being isolated with increasing frequency as a pathogen in oncohematologic patients. Caspofungin and amphotericin B have been reported to have synergistic activity against Fusarium spp. Case presentation We herein report a case of disseminated fusariosis diagnosed by chest CT scan and positive blood cultures to Fusarium spp. Because the patient's clinical condition deteriorated, CRP levels increased, and blood cultures continued to yield Fusarium spp. despite liposomal amphotericin B monotherapy up to 5 mg/kg daily, treatment with caspofungin was added. Within 2 weeks of onset of combined antifungal therapy, the chest CT scan demonstrated a progressive resolution of the pulmonary lesions. Upon discontinuation of intravenous antifungals, the patient received suppressive therapy with oral voriconazole. Three months later, a chest CT scan showed no abnormalities. Twenty-five months after discontinuation of all antifungal therapy, the patient remains in complete remission of her neoplastic disease with no signs of clinical activity of the Fusarium infection. Conclusion This is the first description of successful treatment of disseminated fusariosis in a pediatric patient with acute lymphoblastic leukemia with caspofungin and amphotericin B followed by oral suppressive therapy with voriconazole.

  19. Cost-effectiveness Analysis of Antipsychotic Combination Therapy in Schizophrenia Inpatients

    Directory of Open Access Journals (Sweden)

    Rizky Abdulah

    2017-03-01

    Full Text Available Schizophrenia is one of mental disorders with high cost and lifetime morbidity risk. Hence, it is necessary to analyze the cost-effectiveness of various combinations of antipsychotics. The aim of this study was to analyze the most cost-effective group of antipsychotic combinations in schizophrenia inpatients in West Java Psychiatric Hospital during 2012–2013. Data were collected retrospectively from medical record of patients who used antipsychotics clozapine-haloperidol or clozapine-risperidone therapy. Direct medical costs were obtained from antipsychotics costs, costs of medical treatment, medical expenses, hospitalization costs, and administrative costs. The results showed that the average cost-effectiveness ratio of antipsychotic clozapine-haloperidol was Rp126.898/day and Rp132.781/day for the combination of clozapine-haloperidol and clozapine-risperidone, respectively. Considering length of stay as the therapy effectiveness, it can be concluded that the combination of clozapine-haloperidol is more cost-effective than clozapine-risperidone.

  20. Oxidative stress and mitochondrial dysfunction in infected pregnant

    Directory of Open Access Journals (Sweden)

    Нана Мерабівна Пасієшвілі

    2015-04-01

    Full Text Available The infected pregnant women have been various perinatal complications. The aim of the work was to clarify the role of oxidative stress and mitochondrial dysfunction in the development of perinatal complications in infected pregnant.Methods. The study included 68 pregnant women with signs of maternal-fetal infection (MFI and 30 pregnant women who were found infected (control group. Later pregnant with MFI were divided into 2 groups: the first included 30 women who received traditional antibacterial and antiviral therapy, the second group consisted of 28 women who were additionally given an immunomodulator in combination with ozone therapy.Results. During pregnancy with MFI it is characterized the thrombophilic disorders, break immune homeostasis pregnant, endothelial dysfunction, which adversely affects perinatal indicators.Conclusions. The use of immunomodulators and ozone therapy in the complex treatment of MFI is pathogenetically substantiated effective treatment of oxidative stress and mitochondrial toxicity in the prevention of perinatal complications in infected women

  1. Characteristics of HIV-infected children seen in Western Kenya ...

    African Journals Online (AJOL)

    Subjects: HIV-infected children below age of 15 years seen in a network of 18 clinics in Western Kenya. Interventions: Paediatric HIV diagnosis and care including treatment and prevention of opportunistic infections and provision of combination antiretroviral therapy (CART). Main outcome measures: Diagnosis, clinical ...

  2. Untargeted antifungal therapy in adult patients with complicated intra-abdominal infection

    DEFF Research Database (Denmark)

    Petersen, Marie Warrer; Perner, Anders; Sjövall, Fredrik

    2017-01-01

    who are critically ill have provided conflicting results, and clinical equipoise exists. Accordingly, we aim to assess patient-important benefits and harms of untargeted antifungal therapy versus placebo or no treatment in adult patients with complicated intra-abdominal infection. Methods and analysis......-cause mortality, and secondary outcomes include adverse events, duration of mechanical ventilation and inotropic support, need for renal replacement therapy, emergence of antibiotic resistance and intensive care unit and hospital length-of-stay. Conventional meta-analysis, including sensitivity and subgroup...

  3. Management of infections in rheumatic patients receiving biological therapies. The Portuguese Society of Rheumatology recommendations.

    Directory of Open Access Journals (Sweden)

    Teixeira L

    2016-12-01

    Full Text Available Introduction: Infections are a major cause of morbi dity and mortality in systemic inflammatory rheumatic di - seases and the management of infectious complications in patients under biological therapies deserves parti - cular attention. Objective: Develop evidence-based recommendations for the management of infections in rheumatic patients receiving biological therapies. Methods: A search in PubMed (until 10 November 2014 and EMBASE (until 20 December 2014 databases was performed. Patients with systemic inflammatory rheumatic diseases treated with approved biologics in whom infections occurred were included. Search results were submitted to title and abstract selection, followed by detailed review of suitable studies. Information regarding presentation of the infectious complication, its diagnosis, treatment, and outcome, as well as maintenance or discontinuation of the biological agent was extracted and subsequently pooled according to the type of infection considered. Results of literature review were presented and critically reviewed in a dedi - cated meeting by a multidisciplinary panel. Recommendations were then formulated using the Delphi method. Finally, the level of agreement among rheumatologists was voted using an online survey. Results: Fifteen recommendations were issued. Nine general recommendations concerned the assessment of infectious risk before and while on biologics, the procedures in case of suspected infection and the mana - gement of biologics during infectious complications. Six specific recommendations were developed for respiratory, urinary, gastrointestinal, skin, osteoarticular and disseminated infections. Conclusion: These fifteen recommendations are intended to help rheumatologists in the management of infections in patients on biological therapy. They integrate an extensive literature review, expert opinion and inputs from Portuguese rheumatologists.

  4. Stroke in HIV-infected individuals with and without HCV coinfection in Spain in the combination antiretroviral therapy era

    Science.gov (United States)

    Alvaro-Meca, Alejandro; Díaz, Asunción; Micheloud, Dariela; Aldámiz-Echevarría, Teresa; Fanciulli, Chiara

    2017-01-01

    The incidence of stroke in human immunodeficiency virus (HIV)–infected individuals has been well analyzed in recent epidemiological studies. However, little is known about the specific contribution of hepatitis C virus (HCV) infection to stroke among HIV-infected individuals. The aims of this study were to analyze trends in the incidence rates of stroke in HIV-infected individuals during the combination antiretroviral (cART) era in Spain and to categorize them by the presence or absence of HCV coinfection. We analyzed hospital discharges with a diagnosis of stroke in Spain according to ICD-9-CM during 1997–2013. The study period was divided into four calendar periods (1997–1999, 2000–2003, 2004–2007, and 2008–2013). Patients were classified according to HCV serology. The number of HIV-infected patients was estimated based on data from the National Centre of Epidemiology. We calculated incidence rates (events per 10,000 patient-years) and in-hospital case fatality rates (CFR). The incidence of hemorrhagic stroke (HS) decreased in HIV-monoinfected patients (15.8 [1997–1999] to 6.5 [2008–2013]; P<0.001) and increased in HIV/HCV-coinfected patients (1.3 [1997–1999] to 5.5 [2008–2013]; P<0.001). The incidence of ischemic stroke (IS) decreased in HIV-monoinfected patients (27.4 [1997–1999] to 21.7 [2008–2013]; P = 0.005) and increased in HIV/HCV-coinfected patients (1.8 [1997–1999] to 11.9 [2008–2013]; P<0.001). The CFR was 3.3 times higher for HS than for IS for the whole study period. The CFR of HS in HIV-monoinfected patients decreased significantly (47.4% [1997–1999] to 30.6% [2008–2013]; P = 0.010) but did not change significantly among HIV/HCV-coinfected patients (41.4% [1997–1999] to 44.7% [2008–2013]; P = 0.784). The CFR of IS in the whole HIV-infected population decreased significantly (14.6% [1997–1999] to 10.9% [2008–2013]; P = 0.034), although no significant differences were found when each group was analyzed separately

  5. Distally based saphenous neurocutaneous perforator flap combined with vac therapy for soft tissue reconstruction and hardware salvage in the lower extremities.

    Science.gov (United States)

    Wen, Gen; Wang, Chun-Yang; Chai, Yi-Min; Cheng, Liang; Chen, Ming; Yi-Min, L V

    2013-11-01

    The complex wound with the exposed hardware and infection is one of the common complications after the internal fixation of the tibia fracture. The salvage of hardware and reconstruction of soft tissue defect remain challenging. In this report, we presented our experience on the use of the distally based saphenous neurocutaneous perforator flap combined with vacuum-assisted closure (VAC) therapy for the coverage of the soft tissue defect and the exposed hardware in the lower extremity with fracture. Between January 2008 and July 2010, seven patients underwent the VAC therapy followed by transferring a reversed saphenous neurocutaneous perforator flap for reconstruction of the wound with exposed hardware around the distal tibia. The sizes of the flaps ranged from 6 × 3 cm to 15 × 6 cm. Six flaps survived completely. Partial necrosis occurred in one patient. There were no other complications of repair and donor sites. Bone healing was achieved in all patients. In conclusion, the reversed saphenous neurocutaneous perfortor flaps combined with the VAC therapy might be one of the options to cover the complex wound with exposed hardware in the lower extremities. © 2013 Wiley Periodicals, Inc.

  6. Combined use of Dexa-Scheroson and Primobolan-Depot in radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Nagai, J [Shizuoka Rosai Hospital (Japan)

    1976-05-01

    Dexa-Scheroson and Primobolan-Depot were used together with radiation therapy (Linac therapy) required in 13 cases. The following results were obtained. The decrease in white cell counts, which often occurs in radiation therapy, was inhibited by the drugs. There was no case in which radiation therapy should necessarily withdraw because the number of leuckocytes was decreased to less than 3,000. The patients whose liver function was poor should be treated with both drugs at the beginning of radiation therapy. It was found that the combined use of the drugs is effective in the prevention and the treatment of cerebral edema in radiation therapy of intracranial lesion.

  7. Return-to-health effect of modern combined antiretroviral therapy potentially predisposes HIV patients to hepatic steatosis

    DEFF Research Database (Denmark)

    Mohr, Raphael; Boesecke, Christoph; Dold, Leona

    2018-01-01

    patients underwent CAP determination. Steatosis was classified as S1 (significant steatosis) with CAP > 238 dB/m, S2 with CAP > 260 dB/m, and S3 with CAP > 292 dB/m. Multivariable logistic regression analyses were performed to assess the factors associated with HS in this cohort.Significant HS was detected...... in 118 monoinfected patients (149 in the total cohort). In the total cohort as well as in the monoinfected patients alone, HS grade distribution showed a similar pattern (S1:29%, S2:34%, and S3:37%). Interestingly, patients with HS had a longer history of HIV infection and combined antiretroviral therapy...

  8. EFFECTS OF COMBINATION THERAPY ON PLATELET COUNT IN PATIENTS OF MYOCARDIAL INFARCTION

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    Sadaf Ahmed

    2014-12-01

    Full Text Available Aspirin and clopidogrel are usually used individually to prevent adverse cardiovascular events and stroke. They are used in stabilizing the blood pressure in patients of myocardial infarction while combination therapy of aspirin and Clopidogrel (dual anti-platelet therapy is used for preventing adverse cardiovascular events in myocardial infarction patients. A cross-sectional observational study is conducted through a structured questionnaire from 110 patients of K.I.H.D (Karachi Institute of Heart Disease hospital, Karachi, Pakistan. Indoor/admitted patients with diagnosis of acute coronary syndrome (ACS, non-ST elevation myocardial infarction (NSTE-MI, ST elevation myocardial infarction (STE-MI, supra ventricular tachycardia (SVT were included along with those with previous or current onset of angina pectoris or heart attack. Information from the test reports of these patients was included in the data. Patients without proper test reports were excluded from the study. Combination therapy duration is considered as key tool for evaluation. Out of 100 patients (after exclusion criteria applied almost 18% patients were using the combination therapy for 10 to 25 years while 52% of patients were using the combination therapy for 1 to 10 years. Platelet count of 88% patients was found to be in between 1,50,000–3,50,000/µl. Remaining patients had less than 1,50,000 µl to more than 3,50,000 to 4,50,000 µl. Most frequently reported side effects were chest pain, respiratory issues, headache and depression. On the basis of our data analysis it is concluded that long duration dual anti-platelet therapy will not harm platelet count in human blood but it can create drug dependency in patients. Hypertension is not completely cured with this therapy but can help in stabilizing blood pressure.

  9. Quinolone and glycopeptide therapy for infection in mouse following exposure to mixed-field neutron-γ-photon radiation

    International Nuclear Information System (INIS)

    Brook, I.; Tom, S.P.; Ledney, G.D.

    1993-01-01

    The effects of increased doses of mixed-field neutron-γ-photon irradiation on bacterial translocation and subsequent sepsis, and the influence of antimicrobial therapy on these events, were studied in the C3H/HeN mouse. The results demonstrate a relationship between the doses of mixed-field radiation and the rates of infection due to Enterobacteriaceae. While L-ofloxacin therapy reduces the infection rate, prolongs survival and prevents mortality, the addition of a glycopeptide can enhance systemic infection by resistant bacteria in the irradiated host. (author)

  10. Quinolone and glycopeptide therapy for infection in mouse following exposure to mixed-field neutron-[gamma]-photon radiation

    Energy Technology Data Exchange (ETDEWEB)

    Brook, I. (Naval Medical Research Inst., Bethesda, MD (United States) Armed Forces Radiobiology Research Inst., Bethesda, MD (United States)); Tom, S.P.; Ledney, G.D. (Armed Forces Radiobiology Research Inst., Bethesda, MD (United States))

    1993-12-01

    The effects of increased doses of mixed-field neutron-[gamma]-photon irradiation on bacterial translocation and subsequent sepsis, and the influence of antimicrobial therapy on these events, were studied in the C3H/HeN mouse. The results demonstrate a relationship between the doses of mixed-field radiation and the rates of infection due to Enterobacteriaceae. While L-ofloxacin therapy reduces the infection rate, prolongs survival and prevents mortality, the addition of a glycopeptide can enhance systemic infection by resistant bacteria in the irradiated host. (author).

  11. Possible artemisinin-based combination therapy-resistant malaria in Nigeria: a report of three cases

    Directory of Open Access Journals (Sweden)

    Nnennaya Anthony Ajayi

    2013-07-01

    Full Text Available Artemisinin-based combination therapy-resistant malaria is rare in Sub-Saharan Africa. The World Health Organization identifies monitoring and surveillance using day-3 parasitaemia post-treatment as the standard test for identifying suspected artemisinin resistance. We report three cases of early treatment failure due to possible artemisinin-based combination therapy-resistant Plasmodium falciparum malaria. All cases showed adequate clinical and parasitological responses to quinine. This study reveals a need to re-evaluate the quality and efficacy of artemisinin-based combination therapy agents in Nigeria and Sub-Saharan Africa.

  12. Combined Therapies of Modified Taiyi Miraculous Moxa Roll and Cupping for Patients with Lumbar Intervertebral Disc Herniation.

    Science.gov (United States)

    Cai, Chunyue; Gong, Yuefeng; Dong, Dayong; Xue, Jinbiao; Zheng, Xiaoting; Zhong, Zhangfeng; Shao, Jialong; Mi, Daguo

    2018-01-01

    Lumbar intervertebral disc herniation is a kind of syndrome caused by stimulation or pressure of nerve root and cauda equina due to intervertebral disc disorder, fibrous ring rupture, and pulpiform nucleus protrusion. Application of traditional Chinese medicine (TCM) including acupuncture therapy and cupping therapy is unique and effective treatment for lumbar intervertebral disc herniation in China. Hence, we try to investigate the combined clinical efficacy of modified Taiyi miraculous moxa roll and cupping therapy on patients with lumbar intervertebral disc herniation. Seventy patients were randomly assigned into combined treatment group ( n = 35) and control group ( n = 35). The treatment group received combined therapy of modified Taiyi miraculous moxa roll and cupping therapy, while control group received acupuncture therapy alone. Diagnostic criteria of TCM syndrome, Japanese Orthopedic Association (JOA) score, and simplified McGill pain questionnaire (MPQ) were used to evaluate the therapy. 11 and 13 out of 35 subjects in the combined treatment group had improvement > 75% and between 50% and 75%, respectively. The corresponding number was 2 and 22 of 35 subjects in the acupuncture group. There was significant difference in the clinical efficacy between the treatment group and control group ( P = 0.036). The scores of JOA and MPQ detected in the patients of the two groups ( P cupping therapy or acupuncture. The combined or alone therapies can effectively improve the treatment efficacy in the patients with lumbar intervertebral disc herniation, while the combined therapies show more comparative effectiveness. Furthermore, the combined therapies are potentially safe and cost-effective and also benefit the improvement of short-term pain. Therefore, the combined therapies of the two ancient TCM deserve further clinical applications.

  13. Protease inhibitor associated mutations compromise the efficacy of therapy in human immunodeficiency virus – 1 (HIV-1 infected pediatric patients: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Petrova Anna

    2007-07-01

    Full Text Available Abstract Background Although the introduction of combined therapy with reverse transcriptase and protease inhibitors has resulted in considerable decrease in HIV related mortality; it has also induced the development of multiple drug-resistant HIV-1 variants. The few studies on HIV-1 mutagenesis in HIV infected children have not evaluated the impact of HIV-1 mutations on the clinical, virological and immunological presentation of HIV disease that is fundamental to optimizing the treatment regimens for these patients. Results A cross sectional study was conducted to evaluate the impact of treatment regimens and resistance mutation patterns on the clinical, virological, and immunological presentation of HIV disease in 41 children (25 male and 16 female at the Robert Wood Johnson Pediatric AIDS Program in New Brunswick, New Jersey. The study participants were symptomatic and had preceding treatment history with combined ARV regimens including protease inhibitors (PIs, nucleoside reverse transcriptase inhibitors (NRTIs and non-nucleoside reverse transcriptase inhibitors (NNRTIs. Fifteen (36.6% children were treated with NRTI+NNRTI+ PI, 6 (14.6% with NRTI+NNRTIs, 13 (31.7% with NRTI+PIs, and the remaining 7 (17.1% received NRTIs only. Combined ARV regimens did not significantly influence the incidence of NRTI and NNRTI associated mutations. The duration of ARV therapy and the child's age had no significant impact on the ARV related mutations. The clinico-immunological presentation of the HIV disease was not associated with ARV treatment regimens or number of resistance mutations. However, primary mutations in the protease (PR gene increased the likelihood of plasma viral load (PVL ≥ 10,000 copies/mL irrespective of the child's age, duration of ARV therapy, presence of NRTI and NNRTI mutation. Viremia ≥ 10,000 copies/mL was recorded in almost all the children with primary mutations in the PR region (n = 12/13, 92.3% as compared with only 50.0% (n

  14. Antiviral Therapy by HIV-1 Broadly Neutralizing and Inhibitory Antibodies

    Directory of Open Access Journals (Sweden)

    Zhiqing Zhang

    2016-11-01

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 infection causes acquired immune deficiency syndrome (AIDS, a global epidemic for more than three decades. HIV-1 replication is primarily controlled through antiretroviral therapy (ART but this treatment does not cure HIV-1 infection. Furthermore, there is increasing viral resistance to ART, and side effects associated with long-term therapy. Consequently, there is a need of alternative candidates for HIV-1 prevention and therapy. Recent advances have discovered multiple broadly neutralizing antibodies against HIV-1. In this review, we describe the key epitopes on the HIV-1 Env protein and the reciprocal broadly neutralizing antibodies, and discuss the ongoing clinical trials of broadly neutralizing and inhibitory antibody therapy as well as antibody combinations, bispecific antibodies, and methods that improve therapeutic efficacy by combining broadly neutralizing antibodies (bNAbs with latency reversing agents. Compared with ART, HIV-1 therapeutics that incorporate these broadly neutralizing and inhibitory antibodies offer the advantage of decreasing virus load and clearing infected cells, which is a promising prospect in HIV-1 prevention and treatment.

  15. Sofosbuvir treatment and hepatitis C virus infection

    Science.gov (United States)

    Nakamura, Masato; Kanda, Tatsuo; Haga, Yuki; Sasaki, Reina; Wu, Shuang; Nakamoto, Shingo; Yasui, Shin; Arai, Makoto; Imazeki, Fumio; Yokosuka, Osamu

    2016-01-01

    Hepatitis C virus (HCV) infection is a serious problem worldwide. The use of interferon-based therapy has made HCV eradication challenging. The recent appearance of direct-acting antiviral agents (DAAs) has changed HCV therapy. Combining the use of DAAs with peginterferon and ribavirin has improved treatment efficacy. Furthermore, the combination of different orally administered DAAs has enabled interferon-free therapy with much higher efficacy and safety. In particular, sofosbuvir, a nucleotide-based NS5B inhibitor, prevents HCV RNA synthesis by acting as a “chain terminator”. Treatment with sofosbuvir has attained an extremely high rate of sustained virologic response. The current review summarizes the efficacy and safety of sofosbuvir therapy. PMID:26839641

  16. Description and Demonstration of Cognitive Behavioral Therapy to Enhance Antiretroviral Therapy Adherence and Treat Depression in HIV-Infected Adults.

    Science.gov (United States)

    Newcomb, Michael E; Bedoya, C Andres; Blashill, Aaron J; Lerner, Jonathan A; O'Cleirigh, Conall; Pinkston, Megan M; Safren, Steven A

    2015-11-01

    There are an estimated 1.1 million individuals living with HIV/AIDS in the United States. In addition to the various medical comorbidities of HIV infection, depression is one of the most frequently co-occurring psychiatric conditions among HIV-infected individuals. Furthermore, depression has been found to be associated with nonadherence to antiretroviral therapy (ART), as well as HIV disease progression. Cognitive behavioral therapy (CBT) has repeatedly been found to effectively treat depression in adult populations, and CBT for adherence and depression (CBT-AD) is an effective treatment for improving depressive symptoms and medication adherence in the context of various chronic health conditions, including diabetes and HIV-infection. This paper provides a description of the CBT-AD approach to treat depression and ART adherence in HIV-infected adults, which we have developed and tested in our clinic, and for which detailed therapist and client guides exist. To augment the description of treatment, the present article provides video component demonstrations of several core modules that highlight important aspects of this treatment, including Life-Steps for medication adherence, orientation to CBT-AD and psychoeducation, and suggestions for adaptation of core CBT modules for HIV-infected adults. Discussion of video demonstrations highlights differences in patient presentations and course of treatment between HIV-infected adults receiving CBT-AD and HIV-uninfected adults receiving traditional CBT for depression. This description and the accompanying demonstrations are intended as a practical guide to assist therapists wishing to conduct such a treatment in the outpatient setting.

  17. How to Control HTLV-1-Associated Diseases: Preventing de Novo Cellular Infection Using Antiviral Therapy

    Directory of Open Access Journals (Sweden)

    Amandine Pasquier

    2018-03-01

    Full Text Available Five to ten million individuals are infected by Human T-cell Leukemia Virus type 1 (HTLV-1. HTLV-1 is transmitted through prolonged breast-feeding, by sexual contacts and by transmission of infected T lymphocytes through blood transfusion. One to ten percent of infected carriers will develop a severe HTLV-1-associated disease: Adult-T-cell leukemia/lymphoma (ATLL, or a neurological disorder named Tropical Spastic Paraparesis/HTLV-1 Associated Myelopathy (TSP/HAM. In vivo, HTLV-1 is mostly detected in CD4+ T-cells, and to a lesser extent in CD8+ T cells and dendritic cells. There is a strong correlation between HTLV-1 proviral load (PVL and clinical status of infected individuals. Thus, reducing PVL could be part of a strategy to prevent or treat HTLV-1-associated diseases among carriers. Treatment of ATLL patients using conventional chemotherapy has very limited benefit. Some chronic and acute ATLL patients are, however, efficiently treated with a combination of interferon α and zidovudine (IFN-α/AZT, to which arsenic trioxide is added in some cases. On the other hand, no efficient treatment for TSP/HAM patients has been described yet. It is therefore crucial to develop therapies that could either prevent the occurrence of HTLV-1-associated diseases or at least block the evolution of the disease in the early stages. In vivo, reverse transcriptase (RT activity is low in infected cells, which is correlated with a clonal mode of viral replication. This renders infected cells resistant to nucleoside RT inhibitors such as AZT. However, histone deacetylase inhibitors (HDACi associated to AZT efficiently induces viral expression and prevent de novo cellular infection. In asymptomatic STLV-1 infected non-human primates, HDACi/AZT combination allows a strong decrease in the PVL. Unfortunately, rebound in the PVL occurs when the treatment is stopped, highlighting the need for better antiviral compounds. Here, we review previously used strategies

  18. Targeted photodynamic therapy of established soft-tissue infections in mice

    Science.gov (United States)

    Gad, Faten; Zahra, Touqir; Hasan, Tayyaba; Hamblin, Michael R.

    2004-06-01

    The worldwide rise in antibiotic resistance necessitates the development of novel antimicrobial strategies. Although many workers have used photodynamic therapy (PDT) to kill bacteria in vitro, the use of this approach has seldom been reported in vivo in animal models of infection. We have previously described the first use of PDT to treat excisional wound infections by Gram-negative bacteria in living mice. However these infected wound models used a short time after infection (30 min) before PDT. We now report on the use of PDT to treat an established soft-tissue infection in mice. We used Staphylococcus aureus stably transformed with a Photorhabdus luminescens lux operon (luxABCDE) that was genetically modified to be functional in Gram-positive bacteria. These engineered bacteria emitted bioluminescence allowing the progress of the infection to be monitored in both space and time with a lowlight imaging charged couple device (CCD) camera. One million cells were injected into one or both thigh muscles of mice that had previously been rendered neutropenic by cyclophosphamide administration. Twenty-four hours later the bacteria had multiplied more than one hundred-fold, and poly-L-lysine chlorin(e6) conjugate or free chlorin(e6) was injected into one area of infected muscle and imaged with the CCD camera. Thirty-minutes later red light from a diode laser was delivered as a surface spot or by interstitial fiber into the infection. There was a lightdose dependent loss of bioluminescence (to resistant soft-tissue infections.

  19. Pregnancy Outcomes in HIV-Infected Women Receiving Long-Term Isoniazid Prophylaxis for Tuberculosis and Antiretroviral Therapy

    Directory of Open Access Journals (Sweden)

    Allan W. Taylor

    2013-01-01

    Full Text Available Objective. While 6- to 12-month courses of isoniazid for tuberculosis prevention are considered safe in pregnant women, the effects of longer-term isoniazid prophylaxis or isoniazid in combination with antiretroviral therapy (ART are not established in human-immunodeficiency-virus-(HIV- infected women who experience pregnancy during the course of therapy. Design. Nested study of pregnancy outcomes among HIV-infected women participating in a placebo-controlled, TB-prevention trial using 36 months daily isoniazid. Pregnancy outcomes were collected by interview and record review. Results. Among 196 pregnant women, 103 (52.6% were exposed to isoniazid during pregnancy; all were exposed to antiretroviral drugs. Prior to pregnancy they had received a median of 341 days (range 1–1095 of isoniazid. We observed no isoniazid-associated hepatitis or other severe isoniazid-associated adverse events in the 103 women. Pregnancy outcomes were 132 term live births, 42 premature births, 11 stillbirths, 8 low birth weight, 6 spontaneous abortions, 4 neonatal deaths, and 1 congenital abnormality. In a multivariable model, neither isoniazid nor ART exposure during pregnancy was significantly associated with adverse pregnancy outcome (adjusted odds ratios 0.6, 95% CI: 0.3–1.1 and 1.8, 95% CI 0.9–3.6, resp.. Conclusions. Long-term isoniazid prophylaxis was not associated with adverse pregnancy outcomes, such as preterm delivery, even in the context of ART exposure.

  20. Sorafenib tosylate, Ribavirn and Sofosbuvir combination therapy for HCV virus infected patients with decompensated liver cancer.

    Science.gov (United States)

    Munir, Bushra; Ahmed, Bilal; Kiran, Shumaila; Jalal, Fatima; Zahoor, Muhammad Kashif; Shehzadi, Saba; Oranab, Sadaf; Kamran, Sayed Kashif; Ghaffar, Abdul

    2017-11-01

    Hepatitis C is the most common health problem worldwide and is major cause of death due to proliferation of hepatocellular carcinoma. The medicines available for HCV treatment overcome up-to 95% complications of HCV. However, liver cancer needs some additional care. Normally Sorafenib tosylate 200 mg is recommended for liver cancer. There is no such trial in which this drug could effectively be used in combination of direct acting antivirals for HCV. The study was conducted for HCV patients (n=30) with liver cancer having decompensated stage. Combination of Sorafenib tosylate, Ribavirn and Sofosbuvir were used for the pharmacokinetics of these medicines. Child pugh score less then 7 (CP A) in adults during treatment phase (received 12 weeks of Sorafenib tosylate 200 mg, Ribavirn and Sofosbuvir 400 mg once daily) have no side effect while child pugh score 7-9 (CP B) have evidence of hypertension. The main efficiency end point sustained virology response with overcoming liver cancer as well in 12 weeks after end treatment (SVR-LLC 12). Mean pharmacokinetic exposure to Sorafenib tosylate 200 mg, Ribavirn and Sofosbuvir at week 8th was 2.1, 1.5,1.2 times greater in CP B than in CP A. Adverse effects (AEs) were observed in 12 out of 30 patients but not severe as lethal for life. Treatment with Sorafenib tosylate, Ribavirn and Sofosbuvir for twelve weeks was harmless and well accepted, 100 % patients achieve (SVR LLC 12) with 10-fold cure rate more than previous ones. The combination therapy of Sorafenib tosylate, Ribavirn and Sofosbuvir was found helpful for the management of decompensated liver cancer.

  1. Effect of Smilax China Capsules and azithromycin combined therapy on chronic annexitis

    Directory of Open Access Journals (Sweden)

    Rong-Jun Cong

    2016-11-01

    Full Text Available Objective: To explore the mechanism of Smilax China (Chinese spelling: Jingangteng Capsules and Azithromycin combined therapy for chronic annexitis, and offer help to patients with chronic annexitis on relevant clinical therapies. Methods: A total of 170 cases of patients with chronic annexitis were selected from the gynecological department in our hospital, and randomly divided to be the combination therapy group and the control group by digital table, 85 cases for each group. Patients in control group were treated with Azithromycin. Patients in combination therapy group were treated by giving Smilax China capsules based on the Azithromycin treatment. Relevant indexes of lymphocyte subsets (CD3+ , CD4+ , CD8+ and CD4+ /CD8+ , cytokines (TNF-α, IL-2, IL-6 and IL-10 and hemorheology (blood viscosity, plasma viscosity, hematocrit, red blood cell aggregation index in patients of the two groups were detected before and after treatment. Results: Before treatment, no statistical significance found on the differences of lymphocyte subsets, cytokines and hemorheology between the two groups of patients (P>0.05; After treatment received on the two groups of patients, indexes of CD3+ , CD4+ and CD4+ /CD8+ were dramatically increased, CD8+ , cytokines (TNF-α, IL-2, IL-6 and IL-10 and hemorheology in the combination therapy group were significantly decreased compared with patients in the control group; Statistical significance existed in differences between the two groups (P<0.05. Conclusions: Patients who received Azithromycin therapy added with Smilax China capsules concurrently could be significantly improved levels of lymphocyte subsets, cytokines and hemorheology index. It is of clinical importance for treatment of patients with chronic annexitis.

  2. Neurometabolite Alterations Associated With Cognitive Performance in Perinatally HIV-Infected Children

    NARCIS (Netherlands)

    van Dalen, Yvonne W.; Blokhuis, Charlotte; Cohen, Sophie; ter Stege, Jacqueline A.; Teunissen, Charlotte E.; Kuhle, Jens; Kootstra, Neeltje A.; Scherpbier, Henriette J.; Kuijpers, Taco W.; Reiss, Peter; Majoie, Charles B. L. M.; Caan, Matthan W. A.; Pajkrt, Dasja

    2016-01-01

    Despite treatment with combination antiretroviral therapy (cART), cognitive impairment is still observed in perinatally HIV-infected children. We aimed to evaluate potential underlying cerebral injury by comparing neurometabolite levels between perinatally HIV-infected children and healthy controls.

  3. Cytotect®CP as salvage therapy in patients with CMV infection following allogeneic hematopoietic cell transplantation: a multicenter retrospective study.

    Science.gov (United States)

    Alsuliman, Tamim; Kitel, Caroline; Dulery, Rémy; Guillaume, Thierry; Larosa, Fabrice; Cornillon, Jérôme; Labussière-Wallet, Helene; Médiavilla, Clémence; Belaiche, Stéphanie; Delage, Jeremy; Alain, Sophie; Yakoub-Agha, Ibrahim

    2018-04-13

    Cytomegalovirus is one of the main contributing factors to high mortality rates in patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT). The main factors of treatment failure are both drug resistance and intolerance. In some cases, Cytotect®CP CMV-hyperimmune globulin is used as salvage therapy. This study aims to investigate the safety and efficacy of Cytotect®CP as a salvage therapy in patients with CMV infection after allo-HCT. Twenty-three consecutive patients received Cytotect®CP for CMV infection after prior CMV therapy. At the time of Cytotect®CP introduction, 17 patients (74%) had developed acute GVHD and 15 patients (64%) were receiving steroid treatment; Cytotect®CP was used as monotherapy (n = 7) and in combination (n = 16). Overall, response was observed in 18 patients (78%) with a median time of 15 days (range: 3-51). Of the 18 responders, 4 experienced CMV reactivation, while 5 responders died within 100 days of beginning treatment. Of these 5 deaths, 4 were due to causes unrelated to CMV. Estimated 100-day OS from the introduction of Cytotect®CP was 69.6%. No statistically significant difference was observed in 100-day OS between responders and non-responders (73.7% vs 50.0%, p = 0.258). Cytotect®CP as salvage therapy is effective and well-tolerated. Given its safety profile, early treatment use should be considered.

  4. Colistin-resistant Enterobacteriaceae infections: clinical and molecular characterization and analysis of in vitro synergy.

    Science.gov (United States)

    de Maio Carrillho, Claudia M D; Gaudereto, Juliana J; Martins, Roberta Cristina Ruedas; de Castro Lima, Victor Augusto Camarinha; de Oliveira, Larissa M; Urbano, Mariana R; Perozin, Jamile S; Levin, Anna Sara; Costa, Silvia F

    2017-03-01

    We described 27 polyclonal colistin-resistant Enterobacteriaceae (MIC 4-16 μg/mL) infections (12 pneumonia, 12 urinary tract infection (UTI), two Bacteremia, and one skin/soft tissue infection) in which 74% harbored KPC. The isolates were polyclonal, 6 STs were identified and the colistin resistance was due to chromosome mutations. Eight patients with UTI received monotherapy, and combination therapy was given to 19 patients. Overall mortality was 37%. In vitro synergy using time-kill assay was observed in 14 of 19 (74%) isolates tested; the synergistic effect was observed for almost all isolates for the combination of three drugs: colistin, amikacin, and tigecycline. The Kaplan-Meier survival curve showed no significant difference comparing combination therapy with 2, 3, or more drugs and risk factors associated with death were dialysis and shock. These findings reinforce the fact that colistin in combination with other classes of drugs can be useful in treating infections caused by colistin-resistant CRE. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Combined anti-tumor necrosis factor-α therapy and DMARD therapy in rheumatoid arthritis patients reduces inflammatory gene expression in whole blood compared to DMARD therapy alone

    Directory of Open Access Journals (Sweden)

    Carl K Edwards

    2012-12-01

    Full Text Available Periodic assessment of gene expression for diagnosis and monitoring in rheumatoid arthritis (RA may provide a readily available and useful method to detect subclinical disease progression and follow responses to therapy with disease modifying anti-rheumatic agents (DMARDs or anti-TNF-α therapy. We used quantitative real-time PCR to compare peripheral blood gene expression profiles in active ("unstable" RA patients on DMARDs, stable RA patients on DMARDs, and stable RA patients treated with a combination of a DMARD and an anti-TNF-α agent (infliximab or etanercept to healthy human controls. The expression of 48 inflammatory genes were compared between healthy controls (N=122, unstable DMARD patients (N=18, stable DMARD patients (N=26, and stable patients on combination therapy (N=20. Expression of 13 genes was very low or undetectable in all study groups. Compared to healthy controls, patients with unstable RA on DMARDs exhibited increased expression of 25 genes, stable DMARD patients exhibited increased expression of 14 genes and decreased expression of five genes, and combined therapy patients exhibited increased expression of six genes and decreased expression of 10 genes. These findings demonstrate that active RA is associated with increased expression of circulating inflammatory markers whereas increases in inflammatory gene expression are diminished in patients with stable disease on either DMARD or anti-TNF-α therapy. Furthermore, combination DMARD and anti-TNF-α therapy is associated with greater reductions in circulating inflammatory gene expression compared to DMARD therapy alone. These results suggest that assessment of peripheral blood gene expression may prove useful to monitor disease progression and response to therapy.

  6. Two patterns of cerebral metabolite abnormalities are detected on proton magnetic resonance spectroscopy in HIV-infected subjects commencing antiretroviral therapy

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    Winston, Alan; Taylor-Robinson, Simon D. [Imperial College London, St. Mary' s Hospital, London (United Kingdom); Duncombe, Chris [HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok (Thailand); Li, Patrick C.K. [Queen Elizabeth Hospital, Hong Kong (China); Gill, John M. [Calgary Regional Health Authority, Calgary (Canada); Kerr, Stephen J. [HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok (Thailand); University of New South Wales, National Centre in HIV Epidemiology and Clinical Research, Sydney, NSW (Australia); Puls, Rebekah L.; Emery, Sean; Cooper, David A. [University of New South Wales, National Centre in HIV Epidemiology and Clinical Research, Sydney, NSW (Australia); Collaboration: for the Altair Study Group

    2012-12-15

    Cerebral function impairment remains problematic in subjects with chronic human immunodeficiency virus (HIV) infection despite effective combination antiretroviral therapy (cART). Using cerebral proton magnetic resonance spectroscopy ({sup 1}H MRS), we aimed to determine if abnormalities could be detected in neurologically asymptomatic HIV-infected subjects electively commencing cART. Therapy-naive, HIV-infected individuals and HIV-uninfected controls underwent {sup 1}H MRS in several anatomical voxels including the mid-frontal grey matter (FGM) and right basal ganglia (RBG). Differences in cerebral metabolite ratios between groups and correlations between immune and virological status were assessed. Forty-six subjects were recruited (26 HIV-infected and 20 control subjects). In the HIV-infected group, mean CD4+ count (SD, cells per microlitre) and plasma HIV RNA (SD, log10 copies per millilitre) were 192 (86) and 4.71 (0.64), respectively. Choline (Cho)/Creatine (Cr) and myoinositol (MI)/Cr ratios were significantly lower in the FGM in HIV-infected subjects compared to controls (0.67 (0.14) versus 0.88 (0.49), p = 0.036, and 0.94 (0.28) and 1.17 (0.26), p = 0.008, for Cho/Cr and MI/Cr, respectively) and Cho/Cr ratio associated with CD4+ lymphocyte count (p = 0.041). N-Acetyl-aspartate (NAA)/Cho ratio was significantly lower in the RBG in HIV-infected subjects compared to controls (2.27 (0.54) versus 2.63 (0.68), p = 0.002), and this was associated with greater plasma HIV RNA load (p = 0.014). Two patterns of cerebral metabolite abnormalities were observed in HIV-infected subjects electively commencing cART. Greater inflammatory metabolite ratios (Cho/Cr and MI/Cr) associated with lower markers of peripheral immune markers (CD4+ lymphocyte count) in the FGM and lower neuronal metabolite ratios (NAA/Cho) associated with greater HIV viraemia in the RBG were present in HIV-infected subjects. (orig.)

  7. Treatment of Fournier's Gangrene with Combination of Vacuum-Assisted Closure Therapy, Hyperbaric Oxygen Therapy, and Protective Colostomy

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    Giovanni Zagli

    2011-01-01

    Full Text Available Fournier's gangrene is a rare process which affects soft tissue in the genital and perirectal area. It can also progress to all different stages of sepsis, and abdominal compartment syndrome can be one of its complications. Two patients in septic shock due to Fournier gangrene were admitted to the Intensive Care Unit of Emergency Department. In both cases, infection started from the scrotum and the necrosis quickly involved genitals, perineal, and inguinal regions. Patients were treated with surgical debridement, protective colostomy, hyperbaric oxygen therapy, and broad-spectrum antibacterial chemotherapy. Vacuum-assisted closure (VAC therapy was applied to the wound with the aim to clean, decontaminate, and avoid abdominal compartmental syndrome development. Both patients survived and were discharged from Intensive Care Unit after hyperbaric oxygen therapy cycles and abdominal closure.

  8. [Combined l-thyroxine and l-triiodothyronine replacement therapy in congenital hypothyroidism].

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    Péter, Ferenc; Muzsnai, Agota

    2013-05-12

    L-thyroxine replacement therapy is the treatment of choice for hypothyroidism. Recently, several studies suggested to complete it with l-triiodothyronine in acquired hypothyroidism. To study the role of combined l-thyroxine and l-triiodothyronine therapy in special cases with congenital hypothyroidism. Data of 16 patients (age: 11.9 ± 6.3 years; mean ± SD) are presented who had high serum free thyroxine values or even above the upper limit of reference range (21.16 ± 2.5 pmol/l) together with nonsuppressed TSH levels (15.7 ± 5.7 mIU/l), and therefore received l-triiodothyronine in completion (0.18 ± 0.09 μg/kg) once a day. The combined replacement therapy resulted in a rapid improvement of the hormone parameters (TSH: 4.2 ± 3.15 mIU/l; free thyroxine: 16.55 ± 2.4 and free triiodothyronine: 7.4 ± 1.8 pmol/l). The efficiency of this combined therapy proved to be more evident (TSH: 4.33 ± 3.2 mIU/l; free thyroxine: 16.85 ± 3.1 and free triiodothyronine: 6.4 ± 0.85 pmol/l) in 10 patients treated for a longer period of time (duration of treatment: 2.9 ± 2.0 years). The dose of thyroxine substitution decreased from 2.6 ± 0.9 to 2.18 ± 0.6 μg/kg/day), the ratio of these hormones was between 5:1 and 19:1 and the quotient of free fractions was normalized (3.8 ± 0.4→2.6 ± 0.3) during the replacement therapy. According to the observation of the authors a serious disturbance of feed-back mechanism may develop in some (>5%) children with congenital hypothyroidism (increased TSH release despite elevated free thyroxine level) after normal function of the feed-back system for years. Hormone parameters of these patients improve, then become normal on combined therapy supporting the rationale for this treatment method.

  9. Anaemia in HIV-infected pregnant women receiving triple antiretroviral combination therapy for prevention of mother-to-child transmission: a secondary analysis of the Kisumu breastfeeding study (KiBS).

    Science.gov (United States)

    Odhiambo, Collins; Zeh, Clement; Angira, Frank; Opollo, Valarie; Akinyi, Brenda; Masaba, Rose; Williamson, John M; Otieno, Juliana; Mills, Lisa A; Lecher, Shirley Lee; Thomas, Timothy K

    2016-03-01

    The prevalence of anaemia during pregnancy is estimated to be 35-75% in sub-Saharan Africa and is associated with an increased risk of maternal mortality. We evaluated the frequency and factors associated with anaemia in HIV-infected women undergoing antiretroviral (ARV) therapy for prevention of mother-to-child transmission (PMTCT) enrolled in The Kisumu Breastfeeding Study 2003-2009. Maternal haematological parameters were monitored from 32 to 34 weeks of gestation to 2 years post-delivery among 522 enrolled women. Clinical and laboratory assessments for causes of anaemia were performed, and appropriate management was initiated. Anaemia was graded using the National Institutes of Health Division of AIDS 1994 Adult Toxicity Tables. Data were analysed using SAS software, v 9.2. The Wilcoxon two-sample rank test was used to compare groups. A logistic regression model was fitted to describe the trend in anaemia over time. At enrolment, the prevalence of any grade anaemia (Hb anaemia (Hb anaemia events occurred around delivery (48.8%; n = 20). Anaemia (Hb ≥ 7 and anaemia at delivery (OR 5.87; 95% CI: 4.48, 7.68, P anaemia coincided with clinical malaria (24.4%; n = 10) and helminth (7.3%; n = 3) infections. Resolution of anaemia among most participants during study follow-up was likely related to receipt of ARV therapy. Efforts should be geared towards addressing common causes of anaemia in HIV-infected pregnant women, prioritising initiation of ARV therapy and management of peripartum blood loss. © 2016 John Wiley & Sons Ltd.

  10. Combined Therapies of Modified Taiyi Miraculous Moxa Roll and Cupping for Patients with Lumbar Intervertebral Disc Herniation

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    Chunyue Cai

    2018-01-01

    Full Text Available Lumbar intervertebral disc herniation is a kind of syndrome caused by stimulation or pressure of nerve root and cauda equina due to intervertebral disc disorder, fibrous ring rupture, and pulpiform nucleus protrusion. Application of traditional Chinese medicine (TCM including acupuncture therapy and cupping therapy is unique and effective treatment for lumbar intervertebral disc herniation in China. Hence, we try to investigate the combined clinical efficacy of modified Taiyi miraculous moxa roll and cupping therapy on patients with lumbar intervertebral disc herniation. Seventy patients were randomly assigned into combined treatment group (n=35 and control group (n=35. The treatment group received combined therapy of modified Taiyi miraculous moxa roll and cupping therapy, while control group received acupuncture therapy alone. Diagnostic criteria of TCM syndrome, Japanese Orthopedic Association (JOA score, and simplified McGill pain questionnaire (MPQ were used to evaluate the therapy. 11 and 13 out of 35 subjects in the combined treatment group had improvement > 75% and between 50% and 75%, respectively. The corresponding number was 2 and 22 of 35 subjects in the acupuncture group. There was significant difference in the clinical efficacy between the treatment group and control group (P=0.036. The scores of JOA and MPQ detected in the patients of the two groups (P<0.05 also showed statistically significant differences. Moreover, no serious adverse events occurred in the patients, who received cupping therapy or acupuncture. The combined or alone therapies can effectively improve the treatment efficacy in the patients with lumbar intervertebral disc herniation, while the combined therapies show more comparative effectiveness. Furthermore, the combined therapies are potentially safe and cost-effective and also benefit the improvement of short-term pain. Therefore, the combined therapies of the two ancient TCM deserve further clinical

  11. Current status of the clinical development and implementation of paediatric artemisinin combination therapies in Sub-Saharan Africa.

    Science.gov (United States)

    Agnandji, Selidji Todagbe; Kurth, Florian; Bélard, Sabine; Mombo-Ngoma, Ghyslain; Basra, Arti; Fernandes, José Francisco; Soulanoudjingar, Solange Solmeheim; Adegnika, Akim Ayola; Ramharter, Michael

    2011-10-01

    Timely treatment of infected children with artemisinin based combination therapies is an essential tool for the effective control and potential elimination of malaria. Until recently only tablet formulations have been available for the treatment of children leading to problems of swallowability, palatability and dosing. In consequence, paediatric drug formulations of artemisinin-based combination therapy (ACT) have been developed, showing a clinically significant improvement of tolerability in young children and of their implementation is an increasingly important public health issue. In this mini-review, we focus on the recent development of paediatric ACTs and their use in practice. Paediatric ACTs are formulated as syrup, powder for suspension, dispersible tablets and granules. Overall, the use of paediatric formulation results in an improved management of clinical malaria in young children. To date, only two paediatric ACTs have been certified with WHO prequalification status as an internationally accepted quality standard. Many more paediatric ACTs are available and in use in sub-Saharan Africa despite a lack of publicly available evidence from stringent clinical development programs. The conduct of effectiveness studies to support the introduction of paediatric ACTs in official treatment recommendations is crucial in the global strategy of malaria elimination and quality assurance of available products is a public health priority.

  12. Anti-tumor effects of Egr-IFN gamma gene therapy combined with {sup 125}I-UdR radionuclide therapy

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    Jingguo, Zhao [No.403 Hospital of PLA, Dalian (China); Yanjun, Ni; Xiangfu, Song; Yanyi, Li; Wei, Yang; Ting, Sun; Qingjie, Ma; Fengtong, Gao

    2008-12-15

    Objective: To explore the anti-tumor effects of Egr-IFNgamma gene therapy combined with {sup 125}I-UdR radionuclide therapy in mice bearing H22 hepatocarcinoma and its mechanism. Methods: The recombinant plasmid pcDNAEgr-IFNgamma mixed with liposome was injected into tumor. 48 h later, 370 kBq {sup 125}I-UdR was injected into tumor. The tumor growth rates at different times were observed. After 3 d gene-radionuclide therapy, the concentration of IFNgamma in cytoplasm of H22 cells and cytotoxic activities of splenic CTL of the mice in different groups were examined. Results: The tumor growth rates of pcDNAEgr-IFNgamma + {sup 125}I-UdR group were obviously lower than those of control group, {sup 125}I-UdR group and pcDNAEgr-1 + {sup 125}I-UdR group 6-15 d after gene-radionuclide therapy. IFNgamma protein was found in cytoplasm of H22 cells in pcDNAEgr-IFNgamma + {sup 125}I-UdR group after 3 d gene-radionuclide therapy. Cytotoxic activity of splenic CTL in pcDNAEgr-IFNgamma + {sup 125}I-UdR group was significantly higher than that in the other groups (P<0.01). Conclusions: The anti-tumor effects in vivo of pcDNAEgr-IFNgamma gene therapy combined with {sup 125}I-UdR radionuclide therapy are better than those of {sup 125}I-UdR therapy. (authors)

  13. Dual Therapy Treatment Strategies for the Management of Patients Infected with HIV: A Systematic Review of Current Evidence in ARV-Naive or ARV-Experienced, Virologically Suppressed Patients.

    Science.gov (United States)

    Baril, Jean-Guy; Angel, Jonathan B; Gill, M John; Gathe, Joseph; Cahn, Pedro; van Wyk, Jean; Walmsley, Sharon

    2016-01-01

    We reviewed the current literature regarding antiretroviral (ARV)-sparing therapy strategies to determine whether these novel regimens can be considered appropriate alternatives to standard regimens for the initial treatment of ARV-naive patients or as switch therapy for those patients with virologically suppressed HIV infection. A search for studies related to HIV dual therapy published from January 2000 through April 2014 was performed using Biosis, Derwent Drug File, Embase, International Pharmaceutical Abstracts, Medline, Pascal, SciSearch, and TOXNET databases; seven major trial registries, and the abstracts of major conferences. Using predetermined criteria for inclusion, an expert review committee critically reviewed and qualitatively evaluated all identified trials for efficacy and safety results and potential limitations. Sixteen studies of dual therapy regimens were critiqued for the ARV-naive population. Studies of a protease inhibitor/ritonavir in combination with the integrase inhibitor raltegravir or the nucleoside reverse transcriptase inhibitor lamivudine provided the most definitive evidence supporting a role for dual therapy. In particular, lopinavir/ritonavir or darunavir/ritonavir combined with raltegravir and lopinavir/ritonavir combined with lamivudine demonstrated noninferiority to standard of care triple therapy after 48 weeks of treatment. Thirteen trials were critiqued in ARV-experienced, virologically suppressed patients. The virologic efficacy outcomes were mixed. Although overall data regarding toxicity are limited, when compared with standard triple therapy, certain dual therapy regimens may offer advantages in renal function, bone mineral density, and limb fat changes; however, some dual combinations may elevate lipid or bilirubin levels. The potential benefits of dual therapy regimens include reduced toxicity, improved tolerability and adherence, and reduced cost. Although the data reviewed here provide valuable insights into the

  14. Effects of Hormone Deprivation, 2-Methoxyestradiol Combination Therapy on Hormone-Dependent Prostate Cancer In Vivo

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    Fuminori Sato

    2005-09-01

    Full Text Available 2-Methoxyestradiol (2-ME has potent anti proliferative effects on cancer cells. Its utility alone or in combination with other therapies for treating prostate cancer, however, has not been fully explored. Androgendependent, independent human prostate cancer cells were examined in vivo for their response to combination therapy. Efficacy was assessed by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling assay, measuring microvessel density (MVD in excised tumors. Animals harboring hormonedependent tumors treated with 2-ME alone, androgen deprivation therapy alone, or the combination of the two had a 3.1-fold, 5.3-fold, 10.1-fold increase in apoptosis, respectively. For hormone-independent tumors, treatment with 2-ME resulted in a 2.43-fold increase in apoptosis, a 73% decrease in MVD. 2-ME was most effective against hormone-dependent tumors in vivo, combination therapy resulted in a significant increase in efficacy compared to no treatment controls, trended toward greater efficacy than either 2-ME or androgen deprivation alone. Combination therapy should be investigated further as an additional therapeutic option for early prostate cancer.

  15. Effect of beta-blocker therapy on the risk of infections and death after acute stroke--a historical cohort study.

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    Ilko L Maier

    Full Text Available BACKGROUND: Infections are a frequent cause for prolonged hospitalization and increased mortality after stroke. Recent studies revealed a stroke-induced depression of the peripheral immune system associated with an increased susceptibility for infections. In a mice model for stroke, this immunosuppressive effect was reversible after beta-blocker administration. The aim of our study was to investigate the effect of beta-blocker therapy on the risk of infections and death after stroke in humans. METHODS: 625 consecutive patients with ischemic or hemorrhagic stroke, admitted to a university hospital stroke unit, were included in this historical cohort study. The effect of beta-blocker therapy on post-stroke pneumonia, urinary tract infections and death was investigated using multivariable Poisson and Cox regression models. RESULTS: 553 (88.3% patients were admitted with ischemic stroke, the remaining 72 (11.7% had a hemorrhagic stroke. Median baseline NIHSS was 8 (IQR 5-16 points. 301 (48.2% patients received beta-blocker therapy. There was no difference in the risk of post-stroke pneumonia between patients with and without beta-blocker therapy (Rate Ratio = 1.00, 95%CI 0.77-1.30, p = 0.995. Patients with beta-blocker therapy showed a decreased risk for urinary tract infections (RR = 0.65, 95%CI 0.43-0.98, p = 0.040. 7-days mortality did not differ between groups (Hazard Ratio = 1.36, 95%CI 0.65-2.77, p = 0.425, while patients with beta-blocker therapy showed a higher 30-days mortality (HR = 1.93, 95%CI 1.20-3.10, p = 0.006. CONCLUSIONS: Beta-blocker therapy did not reduce the risk for post-stroke pneumonia, but significantly reduced the risk for urinary tract infections. Different immune mechanisms underlying both diseases might explain these findings that need to be confirmed in future studies.

  16. Effectiveness of cognitive behavioral therapy integrated with systematic desensitization, cognitive behavioral therapy combined with eye movement desensitization and reprocess­ing therapy, and cognitive behavioral therapy combined with virtual reality exposure therapy methods in the treatment of flight anxiety: a randomized trial

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    Triscari MT

    2015-10-01

    Full Text Available Maria Teresa Triscari,1 Palmira Faraci,2 Dario Catalisano,3 Valerio D’Angelo,1 Viviana Urso1 1Laboratory for Psychosomatic Disorders, Local Health Trust, Palermo, Italy; 2Faculty of Human and Social Sciences, University of Enna “Kore”, Enna, Italy; 3Italian Flight Safety Committee, Aeroporto di Fiumicino, Fiumicino (RM, Italy Abstract: The purpose of the research was to compare the effectiveness of the following treatment methods for fear of flying: cognitive behavioral therapy (CBT integrated with systematic desensitization, CBT combined with eye movement desensitization and reprocessing therapy, and CBT combined with virtual reality exposure therapy. Overall, our findings have proven the efficacy of all interventions in reducing fear of flying in a pre- to post-treatment comparison. All groups showed a decrease in flight anxiety, suggesting the efficiency of all three treatments in reducing self-report measures of fear of flying. In particular, our results indicated significant improvements for the treated patients using all the treatment programs, as shown not only by test scores but also by participation in the post-treatment flight. Nevertheless, outcome measures maintained a significant effect at a 1-year follow-up. In conclusion, combining CBT with both the application of eye movement desensitization and reprocessing treatment and the virtual stimuli used to expose patients with aerophobia seemed as efficient as traditional cognitive behavioral treatments integrated with systematic desensitization. Keywords: flight anxiety, fear of flying, aerophobia, cognitive behavioral therapy, EMDR, VRET 

  17. Combined miglustat and enzyme replacement therapy in two patients with type 1 Gaucher disease: two case reports.

    Science.gov (United States)

    Amato, Dominick; Patterson, Mary Anne

    2018-01-27

    Intravenous enzyme replacement therapy is a first-line therapy for Gaucher disease type 1, and substrate reduction therapy represents an oral treatment alternative. Both enzyme replacement therapy and substrate reduction therapy are generally used as monotherapies in Gaucher disease. However, one randomized study and several case reports have described combination therapy over short time periods. We report two female Gaucher disease type 1 patients of mainly Anglo-Saxon descent, where combined enzyme replacement therapy and miglustat substrate reduction therapy were administered to overcome refractory clinical symptoms. The first patient was diagnosed at age 17 and developed Gaucher disease-related bone manifestations that worsened despite starting imiglucerase enzyme replacement therapy. After switching to miglustat substrate reduction therapy, her bone symptoms improved, but she developed tremors and eventually switched back to enzyme replacement therapy. Miglustat was later recommenced in combination with ongoing enzyme replacement therapy due to continued bone pain, and her bone symptoms improved along with maintained visceral manifestations. Enzyme replacement therapy was subsequently tapered off and the patient has since been successfully maintained on miglustat. The second patient was diagnosed aged 3, and commenced imiglucerase enzyme replacement therapy aged 15. After 9 years on enzyme replacement therapy she switched to miglustat substrate reduction therapy and her core symptoms were maintained/stable for 3 years. Imiglucerase enzyme replacement therapy was later added as a boost to therapy and her symptoms were subsequently maintained over a 2.3-year period. However, miglustat was discontinued due to her relocation, necessitating an increase in enzyme replacement therapy dose. Overall, both patients benefited from combination therapy. While the majority of Gaucher disease type 1 patients will not need treatment with both substrate reduction therapy

  18. Combined analgesics in (headache pain therapy: shotgun approach or precise multi-target therapeutics?

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    Fiebich Bernd L

    2011-03-01

    Full Text Available Abstract Background Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix" are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics. Discussion In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect. As an example the fixesd-dose combination of acetylsalicylic acid (ASA, paracetamol (acetaminophen and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy. Summary Multitarget therapeutics like combined analgesics broaden

  19. Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics?

    Science.gov (United States)

    2011-01-01

    Background Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix") are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics. Discussion In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect. As an example the fixesd-dose combination of acetylsalicylic acid (ASA), paracetamol (acetaminophen) and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy. Summary Multitarget therapeutics like combined analgesics broaden the array of therapeutic

  20. Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics?

    Science.gov (United States)

    Straube, Andreas; Aicher, Bernhard; Fiebich, Bernd L; Haag, Gunther

    2011-03-31

    Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix") are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics. In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect.As an example the fixed-dose combination of acetylsalicylic acid (ASA), paracetamol (acetaminophen) and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy. Multitarget therapeutics like combined analgesics broaden the array of therapeutic options, enable the completeness

  1. INFECTIOUS AETIOLOGY OF MARGINAL ZONE LYMPHOMA AND ROLE OF ANTI-INFECTIVE THERAPY

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    Salvatore Perrone

    2016-01-01

    Full Text Available Marginal zone lymphomas have been associated with several infectious agents covering both viral and bacterial pathogens and in some cases a clear aetiological role has been established. Pathogenetic mechanisms are currently not completely understood, however the role of chronic stimulation of the host immune response with persistent lymphocyte activation represents the most convincing explanation for lymphoproliferation. Gastric MALT lymphoma is strictly associated with Helicobacter pylori infection and various eradicating protocols, developed due to increasing antibiotic resistance, represent the first line therapy. The response rate to eradication is good with 80% of response at 1 year; this finding is also noteworthy because recapitulates a cancer cured only by antibacterial approach and it satisfies the Koch postulates of causation, establishing a causative relationship between Hp and gastric MALT lymphoma. Patients with chronic HCV infection have 5 times higher risk to develop MZL, in particular an association with splenic and nodal MZL has been shown in several studies. Moreover, there is evidence of lymphoma regression after antiviral therapy with interferon+ribavirin, thus rising hope that new available drugs, extremely effective against HCV replication, could improve outcome also in HCV-driven lymphomas. The rare cases of MZL localized to orbital fat and eye conjunctivas have been associated with Chlamydia psittaci infection carried by birds. Efficacy of antibacterial therapy against C. psittaci are conflicting and generally poorer thain gastric MALT. Finally some case-reports will cover the relationship between primary cutaneous B-cell Lymphomas and Borrelia Burgdorferi.

  2. Combination Therapy for Airflow Limitation In COPD

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    Jafar Aslani

    2012-08-01

    Full Text Available Background and the purpose of the study Existing evidence confirms that no pharmacologic agent ameliorates the decline in the lung function or changes the prognosis of chronic obstructive pulmonary disease (COPD. We tried a critical combination therapy for management of COPD. Methods Current or past smoker (passive or active COPD patients with moderate to severe COPD who did not respond to primitive therapy (i.e., oral prednisolone (50 mg in the morning for 5 days; with Beclomethasone Fort (3 puff q12h, totally 1500 micrograms/day, Salmeterol (2 puffs q12h, 50 micrograms/puff and ipratropium bromide (4 puffs q8h for two months, enrolled to study. Furthermore they were received N-Acetylcysteine (1200 mg/daily, Azithromycin (tablet 250 mg/every other day and Theophylline (100 mg BD.Results The study group consisted of 44 men and 4 women, with a mean age and standard deviation of 63.6+/-12.7 years (range 22-86 years. Thirteen of 48 patients (27.0% was responder based on 15% increasing in FEV 1 (27.7+/-7.9 after 6.7+/-6.1 months (57.9+/-12.9 year old. There were statistically significant differences in age and smoking between responders and nonresponders (P value was 0.05 and 0.04 respectively. There was no difference in emphysema and air trapping between two groups (p=0.13. Conclusion Interestingly considerable proportion of patients with COPD can be reversible using combination drug therapy and patients will greatly benefit from different and synergic action of the drugs. The treatment was more effective in younger patients who smoke less.

  3. Analysis of the risk of infection in patients with chronic lymphocytic leukemia in the era of novel therapies.

    Science.gov (United States)

    Williams, AnnaLynn M; Baran, Andrea M; Meacham, Philip J; Feldman, Megan M; Valencia, Hugo E; Newsom-Stewart, Catherine; Gupta, Nealansh; Janelsins, Michelle C; Barr, Paul M; Zent, Clive S

    2018-03-01

    We studied the risk of infections in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL). Major infections were defined as requiring hospital admission or intravenous antimicrobial treatment. Incidence rate (IR) ratios (IRR) were used to compare infection rates. Of 263 CLL patients followed for 936.9 person-years, 60% required treatment for progressive CLL (66 received ibrutinib). Infections occurred in 71.9% patients (IR 92.4/100 person-years) with 31.9% having major infections (IR 20.3/100 person-years) and infections causing 37.5% of deaths. CLL treatment was associated with significantly higher risk of major (IRR 3.31, 95% CI 2.10, 5.21) and minor (IRR 1.78, 95% CI 1.43, 2.22) infections. Compared to their previous chemoimmunotherapy patients receiving salvage ibrutinib therapy (n = 47) had a significantly increased risk of a major infection (IRR 2.35 95% CI 1.27, 4.34). The risk of infection in CLL patients remains high even with use of less immunosuppressive therapies.

  4. Human Gongylonema pulchrum Infection: Esophageal Symptoms and Need for Prolonged Albendazole Therapy.

    Science.gov (United States)

    Libertin, Claudia R; Reza, Mohammed; Peterson, Joy H; Lewis, Jason; Hata, D Jane

    2017-04-01

    AbstractWe describe a case of human infection with Gongylonema pulchrum acquired in southeast Georgia. The patient presented with intermittent yet persistent nausea and vomiting for months. This case describes the need for extraction of worms on two occasions each followed by courses of albendazole treatment. Gongylonema pulchrum infections with high worm burden may relapse after extraction of the worm and a 3-day short course of albendazole therapy. Longer courses of albendazole may be indicated in selected circumstances.

  5. Evaluation of follow-up of therapy with fenbendazole incorporated into stabilized liposomes and immunomodulator glucan in mice infected with Toxocara canis larvae.

    Science.gov (United States)

    Hrckova, G; Velebný, S; Obwaller, A; Auer, H; Kogan, G

    2007-01-01

    Anthelmintic activity of benzimidazole carbamate anthelmintics is low against dormant Toxocara canis larvae during late infections in paratenic hosts. The present study was conducted to examine the efficacy of pure fenbendazole, or drug incorporated into sterically stabilized liposomes (SL-FBZ) administered to T. canis-infected mice alone and after its co-administration with the immunomodulator (1-->3)-beta-D-glucan against larvae localized in muscles and brains. Therapy with either drug forms (in total 250 mg/kg in 10 doses) commenced on day 28 post-infection (p.i.) and the efficacy of treatment, examined on day 30 after the last dose of drug, was the highest in groups of mice treated with SL-FBZ in combination with glucan (89.5+/-5.8% in the muscles, 66.1+/-8.1% in brains). During 56 days of follow-up after termination of therapy, serum levels of anti-TES IgG antibodies, circulating IgG-TES immune complexes (CIC) as well as IgG antibodies to the most immunogenic part of recombinant myosin antigen of T. canis larvae were investigated. In contrast to anti-TES IgG antibodies, levels of CIC and anti-myosin antibodies were in the linear correlation with the efficacy of treatments beginning from day 38 post-therapy. We also showed that the serum levels of CIC as well as anti-myosin IgG antibodies seem to be the suitable serological markers for the monitoring of progress in larval destruction and TES resorption from the tissues.

  6. Infections During Induction Therapy of Protocol CCLG-2008 in Childhood Acute Lymphoblastic Leukemia: A Single-center Experience with 256 Cases in China

    Directory of Open Access Journals (Sweden)

    Si-Dan Li

    2015-01-01

    Full Text Available Background: Infections remain a major cause of therapy-associated morbidity and mortality in children with acute lymphoblastic leukemia (ALL. Methods: We retrospectively analyzed the medical charts of 256 children treated for ALL under the CCLG-2008 protocol in Beijing Children′s Hospital. Results: There were 65 infectious complications in 50 patients during vincristine, daunorubicin, L-asparaginase and dexamethasone induction therapy, including microbiologically documented infections (n = 12; 18.5%, clinically documented infections (n = 23; 35.3% and fever of unknown origin (n = 30; 46.2%. Neutropenia was present in 83.1% of the infectious episodes. In all, most infections occurred around the 15 th day of induction treatment (n = 28, and no patients died of infection-associated complications. Conclusions: The infections in this study was independent of treatment response, minimal residual diseases at the end of induction therapy, gender, immunophenotype, infection at first visit, risk stratification at diagnosis, unfavorable karyotypes at diagnosis and morphologic type. The infection rate of CCLG-2008 induction therapy is low, and the outcome of patients is favorable.

  7. Effect of Polycosanol, a grape seed extract and its combined therapy on oxidation markers in rats

    International Nuclear Information System (INIS)

    Oyarzabal Yera, Ambar; Molina Cuevas, Vivian; Jimenez Despaigne, Sonia

    2010-01-01

    The Polycosanol, a mixture of superior primary aliphatic alcohols obtained from the sugarcane wax (Sacharum officinarum, L.) and the grape seeds extract (Vitis vinifera, L.) produces antioxidant effects experimentally and clinically demonstrated. The aim of present paper was to compare the effects of Polycosanol, the grape seed extract, and its combined therapy on oxidative markers in plasma and liver of rats. The rats were distributed into 4 groups: a control one and three treated with Polycosanol, grape seed extract and its combined therapy, respectively, using a 25 mg/kg dose over 4 weeks. The single-therapies significantly reduced the plasmatic concentrations of malonyldialdehyde and of protein-associated carbonyl groups regarding the control, showing a similar efficacy. Combined therapy reduced in a more effective way (p < 0,001) the malonyldialdehyde concentrations of carbonyl groups, and also decreased (p < 0,01) the concentrations of carbonyl groups, but no more than the single-therapies. Each single-therapy reduced the malonyldialdehyde concentrations generated by spontaneous oxidant system in liver homogenate. The effect of combined therapy was higher (p < 0,05) than the grape seed extract, but no more than that of polycosanol. We concluded that oral single-therapies using polycosanol and grape seed extract, administered during 4 weeks, decreased in a similar way, the lipid peroxidation in plasma and liver of rats. Combined therapy was more effective to inhibits the lipid peroxidation in plasma than each single-therapy, separately

  8. Theranostic GO-based nanohybrid for tumor induced imaging and potential combinational tumor therapy.

    Science.gov (United States)

    Qin, Si-Yong; Feng, Jun; Rong, Lei; Jia, Hui-Zhen; Chen, Si; Liu, Xiang-Ji; Luo, Guo-Feng; Zhuo, Ren-Xi; Zhang, Xian-Zheng

    2014-02-12

    Graphene oxide (GO)-based theranostic nanohybrid is designed for tumor induced imaging and potential combinational tumor therapy. The anti-tumor drug, Doxorubicin (DOX) is chemically conjugated to the poly(ethylenimine)-co-poly(ethylene glycol) (PEI-PEG) grafted GO via a MMP2-cleavable PLGLAG peptide linkage. The therapeutic efficacy of DOX is chemically locked and its intrinsic fluorescence is quenched by GO under normal physiological condition. Once stimulated by the MMP2 enzyme over-expressed in tumor tissues, the resulting peptide cleavage permits the unloading of DOX for tumor therapy and concurrent fluorescence recovery of DOX for in situ tumor cell imaging. Attractively, this PEI-bearing nanohybrid can mediate efficient DNA transfection and shows great potential for combinational drug/gene therapy. This tumor induced imaging and potential combinational therapy will open a window for tumor treatment by offering a unique theranostic approach through merging the diagnostic capability and pathology-responsive therapeutic function. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Trigeminal neuralgia: successful antiepileptic drug combination therapy in three refractory cases

    Directory of Open Access Journals (Sweden)

    Prisco L

    2011-08-01

    Full Text Available Lara Prisco1, Mario Ganau2, Federica Bigotto1, Francesca Zornada11Department of Anaesthesiology, Intensive Care and Emergency Medicine, University Hospital of Cattinara, 2Graduate School of Nanotechnology, University of Trieste, ItalyAbstract: Antiepileptic drug combination therapy remains an empirical second-line treatment approach in trigeminal neuralgia, after treatment with one antiepileptic drug or other nonantiepileptic drugs have failed. The results in three patients followed in our clinic are not sufficient to draw definitive conclusions, but suggest the possibility of developing this type of therapeutic approach further.Keywords: trigeminal neuralgia, antiepileptic drugs, combination therapy

  10. [Comparing effectivity of VAC therapy for treatment of infections following arthroplasty or soft-tissue surgery].

    Science.gov (United States)

    Schmal, H; Oberst, M; Hansen, S; Six-Merker, J; Südkamp, N P; Izadpanah, K

    2013-08-01

    Although vacuum-assisted wound closure (VAC) has been developed into a standard technique in septic surgery, reliable data about the efficacy of the treatment are still lacking. Postoperative infections after arthroplasty or soft-tissue surgery were identified using a prospective database for complications (Critical Incidence Reporting System) which was retrospectively supplemented with items for evaluation of VAC therapy. Eradication success of infection was analysed considering epidemiological parameters, course of treatment, and characteristics of causing bacterial strains. Furthermore, serological C-reactive protein (CRP) concentrations were evaluated for diagnostic and prognostic reliability. 92 patients with an average age of 60 ± 4 years were included in the study. Patients with soft tissue infections (STI, n = 53) were statistically significant younger compared to patients with infections following arthroplasty (AI, n = 39) (53 ± 6 vs. 70 ± 4 years; p infected endoprostheses were longer treated on intensive care units (6.1 ± 8.4 vs. 3.5 ± 6.5 days; p infection was with 81 % statistically significant higher in the STI group compared to 38 % in the AI group (p infections in the AI group were associated with a better healing success when compared to chronic infections (p infections (p infection, the probability for eradication of infection was impaired (p infection was reached. CRP values were higher in the AI group and associated with the prognosis (p VAC therapy is higher after soft-tissue infections compared to infections following arthroplasty. Accordingly, mortality is higher in this group. Chronic courses have worse chances for healing in both groups. For serological CRP values a prognostic relevance could be shown. Georg Thieme Verlag KG Stuttgart · New York.

  11. Feasibility Study Combining Art Therapy or Cognitive Remediation Therapy with Family-based Treatment for Adolescent Anorexia Nervosa.

    Science.gov (United States)

    Lock, James; Fitzpatrick, Kathleen Kara; Agras, William S; Weinbach, Noam; Jo, Booil

    2018-01-01

    Adolescents with anorexia nervosa who have obsessive-compulsive (OC) features respond poorly to family-based treatment (FBT). This study evaluated the feasibility of combining FBT with either cognitive remediation therapy (CRT) or art therapy (AT) to improve treatment response in this at-risk group. Thirty adolescents with anorexia nervosa and OC features were randomized to 15 sessions of FBT + CRT or AT. Recruitment rate was 1 per month, and treatment attrition was 16.6% with no differences between groups. Suitability, expectancy and therapeutic relationships were acceptable for both combinations. Correlations between changes in OC traits and changes in cognitive inefficiencies were found for both combinations. Moderate changes in cognitive inefficiencies were found in both groups but were larger in the FBT + AT combination. This study suggests that an RCT for poor responders to FBT because of OC traits combining FBT with either CRT or AT is feasible to conduct. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

  12. Discordant perspectives of rheumatologists and patients on COBRA combination therapy in rheumatoid arthritis.

    NARCIS (Netherlands)

    Tuyl, L.H.D. van; Plass, A.M.C.; Lems, W.F.; Voskuyl, A.E.; Kerstens, P.J.S.M.; Dijkmans, B.A.C.; Boers, M.

    2008-01-01

    Objective. The COBRA therapy (combination therapy in early rheumatoid arthritis) has proven to be an effective treatment for early RA, but is rarely prescribed. A survey showed reluctance of Dutch reumatologists to apply COBRA therapy in early RA. The present qualitative study was carried out to

  13. Negative pressure wound therapy in the management of late deep infections after open reconstruction of achilles tendon rupture.

    Science.gov (United States)

    Mosser, Philipp; Kelm, Jens; Anagnostakos, Konstantinos

    2015-01-01

    Infection is a major complication after open reconstruction of Achilles tendon ruptures. We report on the use of vacuum-assisted closure (VAC) therapy in the treatment of late deep infections after open Achilles tendon reconstruction. Six patients (5 males [83.33%], 1 female [16.67%]; mean age, 52.8 [range 37 to 66] years) were been treated using an identical protocol. Surgical management consisted of debridement, lavage, and necrectomy of infected tendon parts. The VAC therapy was used for local wound preconditioning and infection management. A continuous negative pressure of 125 mm Hg was applied on each wound. For final wound closure, a split-thickness skin graft was performed. The skin graft healing process was also supported by VAC therapy during the first 5 days. The VAC dressings were changed a mean average of 3 (range 1 to 4) times until split-thickness skin grafting could be performed. The mean total duration of the VAC therapy was 13.6 ± 5.9 days. The mean hospital stay was 31.2 ± 15.9 days. No complications with regard to bleeding, seroma, or hematoma formation beneath the skin graft were observed. At a mean follow-up duration of 29.9 (range 4 to 65) months, no re-infection or infection persistence was observed. The VAC device seems to be a valuable tool in the treatment of infected tendons. The generalization of these conclusions should await the results of future studies with larger patient series. Copyright © 2015 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  14. Parvovirus B19 infection in a child with acute lymphoblastic leukemia during induction therapy.

    Science.gov (United States)

    McNall, R Y; Head, D R; Pui, C H; Razzouk, B I

    2001-01-01

    Immunocompromised children, including those undergoing chemotherapy treatment of malignant disease, are at particular risk for infection with parvovirus B19. However, these patients' attenuated immune responses may obscure the serologic and clinical manifestations of the infection. The authors describe a patient undergoing induction therapy for acute lymphoblastic leukemia whose parvovirus B19 infection was identified by the incidental detection of giant pronormoblasts and absence of normal mature erythroid precursors, characteristic of parvovirus infection, on a routine bone marrow examination. Intravenous immunoglobulin was administered and the patient's aplastic anemia resolved completely within 3 weeks. This highlights the importance of alertness to the possibility of parvovirus infection in children with cancer.

  15. Cancer treatment: the combination of vaccination with other therapies

    DEFF Research Database (Denmark)

    Andersen, M.H.; Sorensen, R.B.; Schrama, D.

    2008-01-01

    approach to fight cancer, the combination with additional therapy could create a number of synergistic effects. Herein we discuss the possibilities and prospects of vaccination when combined with other treatments. In this regard, cell death upon drug exposure may be immunogenic or non-immunogenic depending...... and endothelial cells. The efficacy of therapeutic vaccination against cancer will over the next few years be studied in settings taking advantage of strategies in which vaccination is combined with other treatment modalities. These combinations should be based on current knowledge not only regarding the biology...... of the cancer cell per se, but also considering how treatment may influence the malignant cell population as well as the immune system Udgivelsesdato: 2008/11...

  16. Clinical and economic consequences of failure of initial antibiotic therapy for patients with community-onset complicated intra-abdominal infections.

    Directory of Open Access Journals (Sweden)

    Yong Pil Chong

    Full Text Available Complicated intra-abdominal infection (cIAI is infection that extends beyond the hollow viscus of origin into the peritoneal space, and is associated with either abscess formation or peritonitis. There are few studies that have assessed the actual costs and outcomes associated with failure of initial antibiotic therapy for cIAI. The aims of this study were to evaluate risk factors and impact on costs and outcomes of failure of initial antibiotic therapy for community-onset cIAI.A retrospective study was performed at eleven tertiary-care hospitals. Hospitalized adults with community-onset cIAI who underwent an appropriate source control procedure between August 2008 and September 2011 were included. Failure of initial antibiotic therapy was defined as a change of antibiotics due to a lack of improvement of the clinical symptoms and signs associated with cIAI in the first week.A total of 514 patients hospitalized for community-onset cIAI were included in the analysis. The mean age of the patients was 53.3 ± 17.6 years, 72 patients (14% had health care-associated infection, and 48 (9% experienced failure of initial antibiotic therapy. Failure of initial antibiotic therapy was associated with increased costs and morbidity. After adjustment for covariates, patients with unsuccessful initial therapy received an additional 2.9 days of parenteral antibiotic therapy, were hospitalized for an additional 5.3 days, and incurred $3,287 in additional inpatient charges. Independent risk factors for failure of initial antibiotic therapy were health care-associated infection, solid cancer, and APACHE II ≥13.To improve outcomes and costs in patients with community-onset cIAI, rapid assessment of health care-associated risk factors and severity of disease, selection of an appropriate antibiotic regimen accordingly, and early infection source control should be performed.

  17. Effects of adding ribavirin to interferon to treat chronic hepatitis C infection

    DEFF Research Database (Denmark)

    Brok, Jesper; Gluud, Lise L; Gluud, Christian

    2005-01-01

    Evidence shows that a combination therapy of ribavirin plus interferon clears hepatitis C virus from the blood in about 40% of patients with chronic hepatitis C infection, but the effects on clinical outcomes are unclear. We evaluated the beneficial and harmful effects of ribavirin plus interferon...... vs interferon alone for treatment of patients with chronic hepatitis C infection. Randomized trials were included irrespective of blinding, language, or publication status. Trials were identified through the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Library, MEDLINE....... In conclusion, the effect of ribavirin plus interferon on viral clearance may lead to reduced mortality and morbidity in patients with chronic hepatitis C infection. However, combination therapy is associated with increased risk for adverse events....

  18. Association of opioid agonist therapy with lower incidence of hepatitis C virus infection in young adult injection drug users.

    Science.gov (United States)

    Tsui, Judith I; Evans, Jennifer L; Lum, Paula J; Hahn, Judith A; Page, Kimberly

    2014-12-01

    Injection drug use is the primary mode of transmission for hepatitis C virus (HCV) infection. Prior studies suggest opioid agonist therapy may reduce the incidence of HCV infection among injection drug users; however, little is known about the effects of this therapy in younger users. To evaluate whether opioid agonist therapy was associated with a lower incidence of HCV infection in a cohort of young adult injection drug users. Observational cohort study conducted from January 3, 2000, through August 21, 2013, with quarterly interviews and blood sampling. We recruited young adult (younger than 30 years) injection drug users who were negative for anti-HCV antibody and/or HCV RNA. Substance use treatment within the past 3 months, including non-opioid agonist forms of treatment, opioid agonist (methadone hydrochloride or buprenorphine hydrochloride) detoxification or maintenance therapy, or no treatment. Incident HCV infection documented with a new positive result for HCV RNA and/or HCV antibodies. Cumulative incidence rates (95% CI) of HCV infection were calculated assuming a Poisson distribution. Cox proportional hazards regression models were fit adjusting for age, sex, race, years of injection drug use, homelessness, and incarceration. Baseline characteristics of the sample (n = 552) included median age of 23 (interquartile range, 20-26) years; 31.9% female; 73.1% white; 39.7% who did not graduate from high school; and 69.2% who were homeless. During the observation period of 680 person-years, 171 incident cases of HCV infection occurred (incidence rate, 25.1 [95% CI, 21.6-29.2] per 100 person-years). The rate ratio was significantly lower for participants who reported recent maintenance opioid agonist therapy (0.31 [95% CI, 0.14-0.65]; P = .001) but not for those who reported recent non-opioid agonist forms of treatment (0.63 [95% CI, 0.37-1.08]; P = .09) or opioid agonist detoxification (1.45 [95% CI, 0.80-2.69]; P = .23). After adjustment for

  19. HIV drug resistance and hepatitis co-infections in HIV-infected adults and children initiating antiretroviral therapy in Rwanda

    NARCIS (Netherlands)

    Rusine-Bahunde, J.

    2015-01-01

    Since the roll-out of antiretroviral therapy (ART), few data have been generated on outcomes and outcome predictors of ART in adults and children in Rwanda. Equally, the extent of chronic hepatitis virus infections and their impact on the ART outcomes in the country are not known. This information

  20. Therapy of the experimental infection by Strongyloides venezuelensis in rats with injectable ivermectin or levamizole

    Directory of Open Access Journals (Sweden)

    Rubens Campos

    1989-02-01

    Full Text Available For the therapy of human strongyloidiasis, are necessary effective drugs to eliminate both larvae and adult worm parasitism, which may also be used by parenteral route, to obviate the particular conditions presented by many patients. A study based on the experimental infection by Strongyloides venezuelensis in rats was done, administering injectable ivermectin or levamizole. Both drugs were shown to be active, when used in single doses of 0.2 to 0.5 mg/kg of ivermectin, or 26 mg/kg for levamizole. Ivermectin was slightly more effective as far as larval stage of the infection is concerned, and the same happened for levamisole for the adult worm stage. Promising perspectives are visualized to improve the therapy of patients with serious disseminated infection by Strongyloides stercoralis.

  1. An update on emerging therapies for urinary tract infections.

    Science.gov (United States)

    Majeed, Aneela; Alarfaj, Sumaiah; Darouiche, Rabih; Mohajer, Mayar

    2017-03-01

    Urinary tract infections (UTIs) are the most common healthcare-acquired infections, and are associated with high morbidity and mortality. Worldwide use of antibiotics has led to a significant rise in resistant uropathogens emanating from both hospitals and communities. The huge concern of multidrug resistance (MDR) has led the Food and Drug Administration (FDA) to encourage drug companies to invest in the development of new antibiotics. Area covered: In this review we summarized data on already approved antibiotics, and selected emerging therapies that are currently in phase II and III trials with emphasis on complicated urinary tract infections (cUTIs). We performed our search using PubMed, ClinicalTrials.gov, Google Scholar and Pharmaprojects. Expert opinion: Efficacious antimicrobials are needed to overcome MDR organisms. There are several dugs in initial and later stages of development, but most of them lack full spectrum of activity against some Gram-negative organisms, particularly against MDR Pseudomonas aeruginosa. Better understanding of the pathogenesis of UTI and genetic engineering of pathogens can provide new drugs to combat resistance in the future.

  2. Maternal hepatitis C (HCV) infection and Anti-D immunoglobulin therapy: study testing antibodies, RNA and Genotype of HCV in Baghdad.

    Science.gov (United States)

    Al-Kubaisy, Waqar; Daud, Suzanna; Al-Kubaisi, Mustafa Waseem; Al-Kubaisi, Omar Waseem; Abdullah, Nik Nairan

    2018-04-30

    Hepatitis C virus (HCV) infection is a serious health problem. It is a major contributor to end-stage liver disease. Worldwide, 1-8% of all pregnant women were infected. Women with viral hepatitis may be at an increased risk of pregnancy complications. There are several obstetrics intervention acts as risk factors, which are specific to women pertaining the HCV infection; anti-D immunoglobulin (Ig) therapy may be one of them. Our objectives were to estimate the prevalence of HCV antibodies (anti-HCV), RNA, and genotype distribution among women with anti-D Ig therapy. A cross sectional study was conducted. A sample of 154 Rhesus negative (Rh - ve) pregnant women regardless of the anti-D Ig therapy was collected. Anti-HCV were tested using third generation enzyme immunoassay (EIA-3) and immunoblot assay (Lia Tek-111), subsequently. In addition, 89 serum samples were subjected to molecular analysis using RT-PCR and DNA enzyme immunoassay (DEIA) method for the detection of HCV-RNA and genotypes. Anti-HCV, and HCV-RNA seroprevalence were significantly higher (17.1, 35.5%) among women with anti-D Ig than their counter group (6.4, 13.16%), p = .038, .018, respectively. Significant direct positive dose response correlation (r = 0.78, p = .005) had been seen between number of anti-D Ig therapy and anti-HCV seropositive rate. Anti-D Ig therapy act as a risk factor (odds ratio (OR) = 3.01, 95%CI: 1.01-8.9) especially from the third dose onward. Women with anti-D Ig therapy were at higher risk (3.6 times more) of positive HCV-RNA (OR =3.6, 95%CI =1.19-10.837). Genotype HCV-1b showed higher prevalent (52.9%) among the recipients of anti-D Ig therapy while genotype HCV-3a (6.6%) was the lowest. Our study showed that Anti-D immunoglobulin therapy acts as a risk factor for acquiring HCV infection. Screening for HCV should be recommended for all recipients of anti-D Ig. Not only HCV antibodies but HCV-RNA detection being recommended for the diagnosis of HCV

  3. Neurocognitive function in HIV infected patients on antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Alan Winston

    Full Text Available To describe factors associated with neurocognitive (NC function in HIV-positive patients on stable combination antiretroviral therapy.We undertook a cross-sectional analysis assessing NC data obtained at baseline in patients entering the Protease-Inhibitor-Monotherapy-Versus-Ongoing-Triple therapy (PIVOT trial.NC testing comprised of 5 domains. Raw results were z-transformed using standard and demographically adjusted normative datasets (ND. Global z-scores (NPZ-5 were derived from averaging the 5 domains and percentage of subjects with test scores >1 standard deviation (SD below population means in at least two domains (abnormal Frascati score calculated. Patient characteristics associated with NC results were assessed using multivariable linear regression.Of the 587 patients in PIVOT, 557 had full NC results and were included. 77% were male, 68% Caucasian and 28% of Black ethnicity. Mean (SD baseline and nadir CD4+ lymphocyte counts were 553(217 and 177(117 cells/µL, respectively, and HIV RNA was <50 copies/mL in all. Median (IQR NPZ-5 score was -0.5 (-1.2/-0 overall, and -0.3 (-0.7/0.1 and -1.4 (-2/-0.8 in subjects of Caucasian and Black ethnicity, respectively. Abnormal Frascati scores using the standard-ND were observed in 51%, 38%, and 81%, respectively, of subjects overall, Caucasian and Black ethnicity (p<0.001, but in 62% and 69% of Caucasian and Black subjects using demographically adjusted-ND (p = 0.20. In the multivariate analysis, only Black ethnicity was associated with poorer NPZ-5 scores (P<0.001.In this large group of HIV-infected subjects with viral load suppression, ethnicity but not HIV-disease factors is closely associated with NC results. The prevalence of abnormal results is highly dependent on control datasets utilised.ClinicalTrials.gov, NCT01230580.

  4. Cancer Nanomedicine: From Targeted Delivery to Combination Therapy

    Science.gov (United States)

    Xu, Xiaoyang; Ho, William; Zhang, Xueqing; Bertrand, Nicolas; Farokhzad, Omid

    2015-01-01

    The advent of nanomedicine marks an unparalleled opportunity to advance the treatment of a variety of diseases, including cancer. The unique properties of nanoparticles, such as large surface-to volume ratio, small size, the ability to encapsulate a variety of drugs, and tunable surface chemistry, gives them many advantages over their bulk counterparts. This includes multivalent surface modification with targeting ligands, efficient navigation of the complex in vivo environment, increased intracellular trafficking, and sustained release of drug payload. These advantages make nanoparticles a mode of treatment potentially superior to conventional cancer therapies. This article highlights the most recent developments in cancer treatment using nanoparticles as drug-delivery vehicles, including promising opportunities in targeted and combination therapy. PMID:25656384

  5. Spectrum of imaging appearances of intracranial cryptococcal infection in HIV/AIDS patients in the anti-retroviral therapy era

    International Nuclear Information System (INIS)

    Offiah, Curtis E.; Naseer, Aisha

    2016-01-01

    Cryptococcus neoformans infection is the most common fungal infection of the central nervous system (CNS) in advanced human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) patients, but remains a relatively uncommon CNS infection in both the immunocompromised and immunocompetent patient population, rendering it a somewhat elusive and frequently overlooked diagnosis. The morbidity and mortality associated with CNS cryptococcal infection can be significantly reduced by early recognition of the imaging appearances by the radiologist in order to focus and expedite clinical management and treatment. The emergence and evolution of anti-retroviral therapy have also impacted significantly on the imaging appearances, morbidity, and mortality of this neuro-infection. The constellation of varied imaging appearances associated with cryptococcal CNS infection in the HIV and AIDS population in the era of highly active anti-retroviral therapy (HAART) will be presented in this review.

  6. Cancer nanomedicine: gold nanoparticle mediated combined cancer therapy

    Science.gov (United States)

    Yang, C.; Bromma, Kyle; Chithrani, B. D.

    2018-02-01

    Recent developments in nanotechnology has provided new tools for cancer therapy and diagnosis. Among other nanomaterial systems, gold nanoparticles are being used as radiation dose enhancers and anticancer drug carriers in cancer therapy. Fate of gold nanoparticles within biological tissues can be probed using techniques such as TEM (transmission electron microscopy) and SEM (Scanning Electron Microscopy) due to their high electron density. We have shown for the first time that cancer drug loaded gold nanoparticles can reach the nucleus (or the brain) of cancer cells enhancing the therapeutic effect dramatically. Nucleus of the cancer cells are the most desirable target in cancer therapy. In chemotherapy, smart delivery of highly toxic anticancer drugs through packaging using nanoparticles will reduce the side effects and improve the quality and care of cancer patients. In radiation therapy, use of gold nanoparticles as radiation dose enhancer is very promising due to enhanced localized dose within the cancer tissue. Recent advancement in nanomaterial characterization techniques will facilitate mapping of nanomaterial distribution within biological specimens to correlate the radiobiological effects due to treatment. Hence, gold nanoparticle mediated combined chemoradiation would provide promising tools to achieve personalized and tailored cancer treatments in the near future.

  7. Clinical impact of a combined therapy of peritoneal dialysis and hemodialysis.

    Science.gov (United States)

    Matsuo, N; Yokoyama, K; Maruyama, Y; Ueda, Y; Yoshida, H; Tanno, Y; Yamamoto, R; Terawaki, H; Ikeda, M; Hanaoka, K; Yamamoto, H; Ogura, M; Watanabe, S; Kimura, Y; Hosoya, T

    2010-09-01

    Although peritoneal dialysis (PD) is recommended as the first-line treatment for end-stage renal disease, limitations exist to achieving good clinical status when the residual renal function (RRF) has declined. Combined therapy with PD and hemodialysis (HD) is the treatment of choice for patients who cannot control body fluid status and/or cannot obtain adequate solute removal by PD alone. The aim of this study was to evaluate the clinical efficacy of this combined therapy. In this retrospective study, 53 patients on PD and diagnosed with underdialysis and/or overhydration with declining RRF were recruited. Parameters of volume control, uremic solute removal, anemia, and predictors for encapsulating peritoneal sclerosis (EPS) were compared before and 1 year after combined therapy. The patients' hydration status improved significantly with reductions in atrial natriuretic peptide and blood pressure. Serum creatinine and beta2 microglobulin also decreased significantly. The hemoglobin level increased remarkably from 8.2 ± 1.6 to 10.7 ± 1.2 g/dl (p < 0.01) and the reticulocyte count also increased significantly, even though at the same time the dose of recombinant human erythropoietin decreased significantly. The dialysate to plasma creatinine ratio obtained from the fast peritoneal equilibration test (PET) decreased significantly from 0.65 ± 0.11 to 0.59 ± 0.13, and the level of interleukin 6 in PET drainage also significantly decreased. Furthermore, serum C-reactive protein and fibrinogen decreased significantly. Combined therapy with PD and HD is an effective way to control fluid status and to correct inadequate solute removal, leading to improvement in inflammation, peritoneal function and anemia.

  8. Enteric parasitic infection among antiretroviral therapy Naïve HIV-seropositive people: Infection begets infection-experience from Eastern India

    OpenAIRE

    Suman Mitra; Anindya Mukherjee; Dibbendhu Khanra; Ananya Bhowmik; Krishnendu Roy; Arunansu Talukdar

    2016-01-01

    Context: Parasitic opportunistic infections (POIs) frequently occur in HIV/AIDS patients and affect the quality of life. Aims: This study assessing the standard organisms in the stool of HIV-positive patients, their comparison with HIV-negative controls, their relation with various factors, is the first of its kind in the eastern part of India. Settings and Design: hospital-based case?control study. Materials and Methods: A total of 194 antiretroviral therapy na?ve HIV-positive patients (18-6...

  9. HIV-1 CCR5 gene therapy will fail unless it is combined with a suicide gene

    NARCIS (Netherlands)

    Pandit, Aridaman; de Boer, Rob J

    2015-01-01

    Highly active antiretroviral therapy (ART) has successfully turned Human immunodeficiency virus type 1 (HIV-1) from a deadly pathogen into a manageable chronic infection. ART is a lifelong therapy which is both expensive and toxic, and HIV can become resistant to it. An alternative to lifelong ART

  10. Targeting the NF-κB Pathway as a Combination Therapy for Advanced Thyroid Cancer.

    Directory of Open Access Journals (Sweden)

    Nikita Pozdeyev

    Full Text Available NF-κB signaling plays an important role in tumor cell proliferation, cell survival, angiogenesis, invasion, metastasis and drug/radiation resistance. Combination therapy involving NF-κB pathway inhibition is an attractive strategy for the treatment of advanced forms of thyroid cancer. This study was designed to test the efficacy of NF-κB pathway inhibition in combination with cytotoxic chemotherapy, using docetaxel and ionizing radiation in in vitro models of thyroid cancer. We found that while both docetaxel and ionizing radiation activated NF-κB signaling in thyroid cancer cells, there was no synergistic effect on cell proliferation and/or programmed cell death with either genetic (transduction of a dominant negative mutant form of IκBα or pharmacologic (proteasome inhibitor bortezomib and IKKβ inhibitor GO-Y030 inhibition of the NF-κB pathway in thyroid cancer cell lines BCPAP, 8505C, THJ16T and SW1736. Docetaxel plus bortezomib synergistically decreased in vitro invasion of 8505C cells, but not in the other cell lines. Screening of a panel of clinically relevant targeted therapies for synergy with genetic NF-κB inhibition in a proliferation/cytotoxicity assay identified the histone deacetylase (HDAC inhibitor suberoylanilide hydroxamic acid (SAHA as a potential candidate. However, the synergistic effect was confirmed only in the BCPAP cells. These results indicate that NF-κB inhibitors are unlikely to be beneficial as combination therapy with taxane cytotoxic chemotherapy, external radiation therapy or radioiodine therapy. There may be unique circumstances where NF-κB inhibitors may be considered in combination with docetaxel to reduce tumor invasion or in combination with HDAC inhibitors to reduce tumor growth, but this does not appear to be a combination therapy that could be broadly applied to patients with advanced thyroid cancer. Further research may identify which subsets of patients/tumors may respond to this therapeutic

  11. Research progress in combination therapy with pegylated interferon and nucleos(tide analogues in treatment of chronic hepatitis B

    Directory of Open Access Journals (Sweden)

    YU Yiqi

    2015-09-01

    Full Text Available Current antiviral treatment strategy for chronic hepatitis B (CHB includes pegylated interferon (PEG-IFN and nucleos(tide analogues (NAs. Whether combination therapy with PEG-IFN and NAs improve therapeutic efficacy has become the key question regarding the antiviral therapy for CHB. This article reviews the recent progress in combination therapy for the management of CHB. The results indicate that the efficacy of simultaneous combination of PEG-IFN and NAs is not superior to that of PEG-IFN monotherapy in terms of HBeAg seroconversion and response after drug withdrawal. Sequential combination or switching therapy in PEG-IFN- or NAs-treated patients, as well as combination with immune cell therapy, is a promising treatment strategy.

  12. Combination use of lentinan with x-ray therapy in mouse experimental tumor system, (3). Combination effect on the metastatic tumors

    Energy Technology Data Exchange (ETDEWEB)

    Shiio, Tsuyoshi; Ohishi, Kazuo; Niitsu, Iwayasu; Hayashibara, Hiromi; Tsuchiya, Yoshiharu; Yoshihama, Takashi; Moriyuki, Hirobumi

    1988-03-01

    Combination effect of lentinan with X-ray irradiation on the metastatic mouse tumors, L1210, KLN205 and Lewis lung carcinoma were studied. Combination use of lentinan with X-ray therapy prolonged the life of BDF/sub 1/ mice bearing L1210 leukemia in the suitable combination conditions. Combination effects of lentinan with X-ray therapy were also observed on the suppression of the growth of KLN205 squamus cell carcinoma and on the suppression of the metastasis of Lewis lung carcinoma. Especially, in the case that lentinan was administered before or after X-ray local irradiation in the pulmorary metastasis system of Lewis lung carcinoma, a marked suppressin of pulmonary metastasis was observed and 2 to 4 mice among 8 tested mice were tumor free.

  13. Computational Study to Determine When to Initiate and Alternate Therapy in HIV Infection

    Directory of Open Access Journals (Sweden)

    Matthias Haering

    2014-01-01

    Full Text Available HIV is a widespread viral infection without cure. Drug treatment has transformed HIV disease into a treatable long-term infection. However, the appearance of mutations within the viral genome reduces the susceptibility of HIV to drugs. Therefore, a key goal is to extend the time until patients exhibit resistance to all existing drugs. Current HIV treatment guidelines seem poorly supported as practitioners have not achieved a consensus on the optimal time to initiate and to switch antiretroviral treatments. We contribute to this discussion with predictions derived from a mathematical model of HIV dynamics. Our results indicate that early therapy initiation (within 2 years postinfection is critical to delay AIDS progression. For patients who have not received any therapy during the first 3 years postinfection, switch in response to virological failure may outperform proactive switching strategies. In case that proactive switching is opted, the switching time between therapies should not be larger than 100 days. Further clinical trials are needed to either confirm or falsify these predictions.

  14. Negative pressure wound therapy for the treatment of infected wounds with exposed knee joint after patellar fracture.

    Science.gov (United States)

    Lee, Sang Yang; Niikura, Takahiro; Miwa, Masahiko; Sakai, Yoshitada; Oe, Keisuke; Fukazawa, Takahiro; Kawakami, Yohei; Kurosaka, Masahiro

    2011-06-14

    Treatment of soft tissue defects with exposed bones and joints, resulting from trauma, infection, and surgical complications, represents a major challenge. The introduction of negative pressure wound therapy has changed many wound management practices. Negative pressure wound therapy has recently been used in the orthopedic field for management of traumatic or open wounds with exposed bone, nerve, tendon, and orthopedic implants. This article describes a case of a patient with a large soft tissue defect and exposed knee joint, in which negative pressure wound therapy markedly improved wound healing. A 50-year-old man presented with an ulceration of his left knee with exposed joint, caused by severe wound infections after open reduction and internal fixation of a patellar fracture. After 20 days of negative pressure wound therapy, a granulated wound bed covered the exposed bones and joint.To our knowledge, this is the first report of negative pressure wound therapy used in a patient with a large soft tissue defect with exposed knee joint. Despite the chronic wound secondary to infection, healing was achieved through the use of the negative pressure wound therapy, thus promoting granulation tissue formation and closing the joint. We suggest negative pressure wound therapy as an alternative option for patients with lower limb wounds containing exposed bones and joints when free flap transfer is contraindicated. Our result added to the growing evidence that negative pressure wound therapy is a useful adjunctive treatment for open wounds around the knee joint. Copyright 2011, SLACK Incorporated.

  15. Adenovirus-mediated IL-12 gene therapy in combination with radiotherapy for murine liver cancer

    International Nuclear Information System (INIS)

    Wei Daoyan; Dai Bingbing; Wang Zhonghe; Chen Shishu

    2001-01-01

    Objective: To investigate the synergistic antitumor effects of adenovirus-mediated IL-12 gene therapy in combination with radiotherapy in mice bearing liver cancer. Methods: Balb/c mice bearing liver cancer received the treatment at day 1 with tumor local irradiation (TLI) of 20 Gy or mask irradiation when tumor size reached 0.6-1.0 cm. Within 1 hour after irradiation, adenovirus containing IL-12 gene or PBS was intra-tumor injected once a week. Forty-eight hours after the second injection, IFN-γ levels in sera and the supernatant of cultured spleen cells were assayed by ELISA, CTL activity of spleen cells was measured by 3 H-TdR release assay, and phenotypes of tumor-infiltrating lymphocytes were analysed by immunohistochemical staining. Results: The growth of tumors in animals treated with a combination of IL-12 gene therapy and TLI was inhibited more significantly than those with either single treatment (P + and CD8 + lymphocyte infiltration and tumor-specific cytolytic activities, and the levels of IFN-γ in sera were higher in IL-12 gene therapy and IL-12 gene therapy combined with TLI groups. Conclusion: These results suggest that IL-12 gene therapy combined with radiotherapy is more effective than both single treatment modalities and can induce specific antitumor immuno-response greatly

  16. Combination photodynamic therapy of human breast cancer using salicylic acid and methylene blue

    Science.gov (United States)

    Hosseinzadeh, Reza; Khorsandi, Khatereh; Jahanshiri, Maryam

    2017-09-01

    The objective of this study was to evaluate the effects of combination therapy with methylene blue (MB) assisted photodynamic therapy (PDT) and salicylic acid (SA) as chemo-therapy anticancer agent. The binding of salicylic acid to methylene blue was studied using spectrophotometric method. The results show the 1:2 complex formation between SA and MB. The binding constants and related Gibbs free energies o are obtained (Kb1 = 183.74, Kb2 = 38.13 and ∆ Gb1° = 12.92 kJ·mol- 1, ∆ Gb2° =9.02 kJ·mol- 1). The spectrophotometric results show the improvement in solubilization and reduction prevention for SA and MB in the complex form. These results are in agreements with cellular experiments. The dark toxicity measurements represent the improve efficacy of chemotherapy using combination of SA and MB. The photodynamic therapy results (using red LED as light source (630 nm; power density: 30 mW cm- 2)) show that the cancer cell killing efficiency of MB increases in the combination with SA due to reduction prevention and stabilization of monomeric form of MB.

  17. Ganciclovir-Resistant Cytomegalovirus Infection in a Kidney Transplant Recipient Successfully Treated with Foscarnet and Everolimus.

    Science.gov (United States)

    Menghi, Viola; Comai, Giorgia; Baraldi, Olga; Liviano D'Arcangelo, Giovanni; Lazzarotto, Tiziana; La Manna, Gaetano

    2016-01-01

    Cytomegalovirus (CMV) infection remains a major cause of morbidity, graft failure, and death in kidney transplant recipients. We describe a case of a 53-year-old CMV-seronegative man who underwent renal transplant from a CMV-positive donor and who developed ganciclovir- (GCV-) resistant CMV infection. Foscarnet was started while immunosuppressive therapy was modified with the introduction of everolimus minimizing tacrolimus dosage. Only two weeks after the start of this treatment regimen was the patient's viral load negative. At two-year follow-up the patient has no clinical or laboratory signs of CMV infection and a good and stable renal function or graft survival. In our case, administration of an mTOR inhibitor combined with foscarnet led to rapid and persistent viral clearance without compromising short- and medium-term graft function. This combination therapy supports the need for the kidney transplant community to individualize a target therapy for each type of GCV-resistant CMV infection.

  18. Combined aquaretic and diuretic therapy in acute heart failure

    Directory of Open Access Journals (Sweden)

    Goyfman M

    2017-06-01

    Full Text Available Michael Goyfman,1 Paul Zamudio,2 Kristine Jang,3 Jennifer Chee,3 Catherine Miranda,2 Javed Butler,1 Nand K Wadhwa2 1Division of Cardiology, 2Division of Nephrology, 3Department of Medicine, Stony Brook School of Medicine, Stony Brook, NY, USA Introduction: Acute heart failure (AHF is a leading cause of hospitalization and readmission in the US. The present study evaluated maximum diuresis while minimizing electrolyte imbalances, hemodynamic instability, and kidney dysfunction, to achieve a euvolemic state safely in a shorter period of time.Methods and results: A protocol of combined therapy with furosemide, metolazone, and spironolactone, with or without tolvaptan and acetazolamide, was used in 17 hospitalized patients with AHF. The mean number of days on combination diuretic protocol was 3.8 days. The mean daily fluid balance was 3.0±2.1 L negative. The mean daily urine output (UOP was 4.1±2.0 L (range 1.8–10.5 L. There were minimal fluctuations in serum electrolyte levels and serum creatinine over the duration of diuretic therapy. There was no statistically significant change in patients’ creatinine from immediately prior to therapy to the last day of therapy, with a mean increase in creatinine of 0.14 mg/dL (95% CI −0.03, +0.30, p=0.10.Conclusion: Our strategy of treating AHF by achieving high UOP, while maintaining stable electrolytes and creatinine in a short period to euvolemic state, is safe. Keywords: diuretics, aquaretic, acute heart failure, volume overload

  19. 5-aminolevulinic acid-mediated photodynamic therapy and its strain-dependent combined effect with antibiotics on Staphylococcus aureus biofilm.

    Directory of Open Access Journals (Sweden)

    Qing-Zhao Zhang

    Full Text Available Staphylococcus aureus (S. aureus is hard to be eradicated, not only due to the emergence of antibiotic resistant strains but also because of its ability to form biofilm. Antibiotics are the major approach to treating biofilm infections, but their effects are unsatisfactory. One of the potential alternative treatments for controlling biofilm infections is photodynamic therapy (PDT, which requires the administration of photosensitizer, followed by light activation. 5-aminolevulinic acid (ALA, a natural photosensitizer prodrug, presents favorable characteristics, such as easy penetration and rapid clearance. These advantages enable ALA-based PDT (ALA-PDT to be well-tolerated by patients and it can be repeatedly applied without cumulative toxicity or serious side effects. ALA-PDT has been proven to be an effective treatment for multidrug resistant pathogens; however, the study of its effect on S. aureus biofilm is limited. Here, we established our PDT system based on the utilization of ALA and a light-emitting diode, and we tested the effect of ALA-PDT on S. aureus biofilm as well as the combined effect of ALA-PDT and antibiotics on S. aureus biofilm. Our results showed that ALA-PDT has a strong antibacterial effect on S. aureus biofilm, which was confirmed by the confocal laser scanning microscope. We also found that lethal photosensitization occurred predominantly in the upper layer of the biofilm, while the residual live bacteria were located in the lower layer of the biofilm. In addition, the improved bactericidal effect was observed in the combined treatment group but in a strain-dependent manner. Our results suggest that ALA-PDT is a potential alternative approach for future clinical use to treat S. aureus biofilm-associated infections, and some patients may benefit from the combined treatment of ALA-PDT and antibiotics, but drug sensitivity testing should be performed in advance.

  20. Combination therapy with dutasteride and tamsulosin for the treatment of symptomatic enlarged prostate

    Science.gov (United States)

    Miller, J; Tarter, TH

    2009-01-01

    Benign prostatic hyperplasia (BPH) is a frequent cause of lower urinary symptoms, with a prevalence of 50% by the sixth decade of life. Hyperplasia of stromal and epithelial prostatic elements that surround the urethra cause lower urinary tract symptoms (LUTS), urinary tract infection and acute urinary retention. Medical treatments of symptomatic BPH include; 1) the 5α-reductase inhibitors, 2) the α1-adrenergic antagonists, and 3) the combination of a 5α-reductase inhibitor and a α1-adrenergic antagonist. Selective α1-adrenergic antagonists relax the smooth muscle of the prostate and bladder neck without affecting the detrussor muscle of the bladder wall, thus decreasing the resistance to urine flow without compromising bladder contractility. Clinical trials have shown that α1-adrenergic antagonists decrease LUTS and increase urinary flow rates in men with symptomatic BPH, but do not reduce the long-term risk of urinary retention or need for surgical intervention. Inhibitors of 5α-reductase decrease production of dihydrotestosterone within the prostate resulting in decreased prostate volumes, increased peak urinary flow rates, improvement of symptoms, and decreased risk of acute urinary retention and need for surgical intervention. Interim results of the ongoing Combination of Avodart and Tamsulosin (CombAt) study have shown combination therapy with the 5α-reductase inhibitor dutasteride and the α1-adrenergic antagonist tamsulosin offer significant improvements from baseline compared with either drug alone. PMID:19554096

  1. Screening prior to biological therapy in Crohn's disease: adherence to guidelines and prevalence of infections. Results from a multicentre retrospective study

    NARCIS (Netherlands)

    van der Have, Mike; Belderbos, Tim D. G.; Fidder, Herma H.; Leenders, Max; Dijkstra, Gerard; Peters, Charlotte P.; Eshuis, Emma J.; Ponsioen, Cyriel Y.; Siersema, Peter D.; van Oijen, Martijn G. H.; Oldenburg, Bas

    2014-01-01

    Screening for opportunistic infections prior to starting biological therapy in patients with inflammatory bowel disease is recommended. To assess adherence to screening for opportunistic infections prior to starting biological therapy in Crohn's disease patients and its yield. A multicentre

  2. Screening prior to biological therapy in Crohn's disease : Adherence to guidelines and prevalence of infections. Results from a multicentre retrospective study

    NARCIS (Netherlands)

    van der Have, Mike; Belderbos, Tim D. G.; Fidder, Herma H.; Leenders, Max; Dijkstra, Gerard; Peters, Charlotte P.; Eshuis, Emma J.; Ponsioen, Cyriel Y.; Siersema, Peter D.; van Oijen, Martijn G. H.; Oldenburg, Bas

    2014-01-01

    Background: Screening for opportunistic infections prior to starting biological therapy in patients with inflammatory bowel disease is recommended. Aims: To assess adherence to screening for opportunistic infections prior to starting biological therapy in Crohn's disease patients and its yield.

  3. Building a roadmap for developing combination therapies for Alzheimer's disease.

    Science.gov (United States)

    Perry, Daniel; Sperling, Reisa; Katz, Russell; Berry, Donald; Dilts, David; Hanna, Debra; Salloway, Stephen; Trojanowski, John Q; Bountra, Chas; Krams, Michael; Luthman, Johan; Potkin, Steven; Gribkoff, Val; Temple, Robert; Wang, Yaning; Carrillo, Maria C; Stephenson, Diane; Snyder, Heather; Liu, Enchi; Ware, Tony; McKew, John; Fields, F Owen; Bain, Lisa J; Bens, Cynthia

    2015-03-01

    Combination therapy has proven to be an effective strategy for treating many of the world's most intractable diseases. A growing number of investigators in academia, industry, regulatory agencies, foundations and advocacy organizations are interested in pursuing a combination approach to treating Alzheimer's disease. A meeting co-hosted by the Accelerate Cure/Treatments for Alzheimer's Disease Coalition, the Critical Path Institute and the Alzheimer's Association addressed challenges in designing clinical trials to test multiple treatments in combination and outlined a roadmap for making such trials a reality.

  4. Well-established and more recent aspects of combined therapy of gynaecological tumours

    International Nuclear Information System (INIS)

    Ladner, H.A.

    1981-01-01

    The question of superiority concerning operative or radiation therapy should not make us forget that the combined therapy of gynaecologic carcinomas was proven to be good. The differing therapy results are due to the problems of classifying the phases, the ages of the patients, the histology, and, not less important, the radiation sensibility of gynaecologic tumours. The psychological and psychosomatic aspects of treating gynaecologic tumours are discussed. (APR) [de

  5. Smart activatable and traceable dual-prodrug for image-guided combination photodynamic and chemo-therapy.

    Science.gov (United States)

    Hu, Fang; Yuan, Youyong; Mao, Duo; Wu, Wenbo; Liu, Bin

    2017-11-01

    Activatable photosensitizers (PSs) and chemo-prodrugs are highly desirable for anti-cancer therapy to reduce systemic toxicity. However, it is difficult to integrate both together into a molecular probe for combination therapy due to the complexity of introducing PS, singlet oxygen quencher, chemo-drug, chemo-drug inhibitor and active linker at the same time. To realize activatable PS and chemo-prodrug combination therapy, we develop a smart therapeutic platform in which the chemo-prodrug serves as the singlet oxygen quencher for the PS. Specifically, the photosensitizing activity and fluorescence of the PS (TPEPY-SH) are blocked by the chemo-prodrug (Mitomycin C, MMC) in the probe. Meanwhile, the cytotoxicity of MMC is also inhibited by the electron-withdrawing acyl at the nitrogen position next to the linker. Upon glutathione activation, TPEPY-S-MMC can simultaneously release active PS and MMC for combination therapy. The restored fluorescence of TPEPY-SH is also used to report the activation for both PS and MMC as well as to guide the photodynamic therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Plasma metabolic changes in Chinese HIV-infected patients receiving lopinavir/ritonavir based treatment: Implications for HIV precision therapy.

    Science.gov (United States)

    Li, Xiaolin; Wu, Tong; Jiang, Yongjun; Zhang, Zining; Han, Xiaoxu; Geng, Wenqing; Ding, Haibo; Kang, Jing; Wang, Qi; Shang, Hong

    2018-05-16

    The goal of this study is to profile the metabolic changes in the plasma of HIV patients receiving lopinavir/ritonavir (LPV/r)-based highly active antiretroviral therapy (HAART) relative to their treatment-naïve phase, aimed to identify precision therapy for HIV for improving prognosis and predicting dyslipidemia caused by LPV/r. 38 longitudinal plasma samples were collected from 19 HIV-infected patients both before and after antiretroviral therapy, and 18 samples from healthy individuals were used as controls. Untargeted metabolomics profiling of these plasma samples was performed using liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). A total of 331 compounds of known identity were detected among these metabolites, a 67-metabolite signature mainly mapping to tryptophan, histidine, acyl carnitine, ketone bodies and fatty acid metabolism distinguished HIV patients from healthy controls. The levels of 19 out of the 67 altered metabolites including histidine, kynurenine, and 3-hydroxybutyrate (BHBA), recovered after LPV/r-based antiretroviral therapy, and histidine was positively correlated with the presence of CD4 + T lymphocytes. Furthermore, using receiver operating characteristic (ROC) analyses, we discovered that butyrylcarnitine in combination with myristic acid from plasma in treatment-naïve patients could predict dyslipidemia caused by LPV/r with 87% accuracy. Metabolites alterations in treatment-naïve HIV patients may indicate an inflammatory, oxidative state and mitochondrial dysfunction that is permissive for disease progression. Histidine may provide a specific protective function for HIV patients. Besides, elevated fatty acids levels including butyrylcarnitine and myristic acid after infection may indicate patients at risk of suffering from dyslipidemia after LPV/r-based HAART. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Effects of massage therapy on anxiety, depression, hyperventilation and quality of life in HIV infected patients: A randomized controlled trial.

    Science.gov (United States)

    Gregory, Reychler; Caty, Gilles; Aude, Arcq; Laurie, Lebrun; Leïla, Belkhir; Jean-Cyr, Yombi; Jean-Christophe, Marot

    2017-06-01

    HIV infection is often preceded or accompanied by psychiatric comorbidities. These disorders improve with complementary therapies. The aim of this study was to measure the effect of massage therapy on anxiety, depression, hyperventilation and quality of life in HIV infected patients. Adult HIV-infected patients were randomized (n=29) in massage therapy group (one hour a week during four weeks) and control group. Anxiety and depression (HADS-A and HADS-D), hyperventilation (Nijmegen questionnaire) and quality of life (WHOQOL-HIV) were evaluated at inclusion and after 4 weeks. At inclusion, 51% and 17% of the patients had a positive HADS-A and HADS-D score respectively. Two facets from WHOQOL-HIV ("Home environment" and "Death and dying" (p=0.04)) were different between groups. After the four week massage therapy, a significant improvement was observed only for Nijmegen questionnaire (p=0.01) and HADS-A (p=0.04) contrarily to WHOQOL-HIV and HADS-D. Domains of the WHOQOL-HIV did not improve following the massage therapy. Only "Pain and discomfort" facet improved after massage therapy (p=0.04). This study highlights the positive impact of a four week massage therapy on anxiety and hyperventilation in HIV infected patients. However, neither benefit of this program was observed on depression and quality of life. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Dynamics of tumor growth and combination of anti-angiogenic and cytotoxic therapies