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1. Notulae to the Italian alien vascular flora: 14

Author

Galasso, G, Domina, G, Andreatta, S, Argenti, C, Astuti, G, Bacaro, G, Bacchetta, G, Bagella, S, Banfi, E, Barberis, D, Bartolucci, F, Bernardo, L, Bonari, G, Brundu, G, Buccomino, G, Calvia, G, Cancellieri, L, Capuano, A, Celesti-Grapow, L, Conti, F, Cuena-Lombraña, A, D’Amico, F, De Fine, G, de Simone, L, Guacchio, E, Emili, F, Fanfarillo, E, Fascetti, S, Fiaschi, T, Fois, M, Fortini, P, Gentili, R, Giardini, M, Hussain, A, Iamonico, D, Laface, V, Lallai, A, Lazzaro, L, Lecis, A, Ligato, E, Loi, G, Lonati, M, Lozano, V, Maccherini, S, Mainetti, A, Mascia, F, Mei, G, Menini, F, Merli, M, Montesano, A, Mugnai, M, Musarella, C, Nota, G, Olivieri, N, Passalacqua, N, Pinzani, L, Pisano, A, Pittarello, M, Podda, L, Posillipo, G, Potenza, G, Probo, M, Prosser, F, Quaglini, L, Enri, S, Rivieccio, G, Roma-Marzio, F, Rosati, L, Selvaggi, A, Soldano, A, Stinca, A, Tasinazzo, S, Tassone, S, Terzi, M, Vallariello, R, Vangelisti, R, Verloove, F, Lastrucci, L, Galasso G., Domina G., Andreatta S., Argenti C., Astuti G., Bacaro G., Bacchetta G., Bagella S., Banfi E., Barberis D., Bartolucci F., Bernardo L., Bonari G., Brundu G., Buccomino G., Calvia G., Cancellieri L., Capuano A., Celesti-Grapow L., Conti F., Cuena-Lombraña A., D’Amico F. S., De Fine G., de Simone L., Guacchio E. D., Emili F., Fanfarillo E., Fascetti S., Fiaschi T., Fois M., Fortini P., Gentili R., Giardini M., Hussain A. N., Iamonico D., Laface V. L. A., Lallai A., Lazzaro L., Lecis A. P., Ligato E., Loi G., Lonati M., Lozano V., Maccherini S., Mainetti A., Mascia F., Mei G., Menini F., Merli M., Montesano A., Mugnai M., Musarella C. M., Nota G., Olivieri N., Passalacqua N. G., Pinzani L., Pisano A., Pittarello M., Podda L., Posillipo G., Potenza G., Probo M., Prosser F., Quaglini L. A., Enri S. R., Rivieccio G., Roma-Marzio F., Rosati L., Selvaggi A., Soldano A., Stinca A., Tasinazzo S., Tassone S., Terzi M., Vallariello R., Vangelisti R., Verloove F., Lastrucci L., Galasso, G, Domina, G, Andreatta, S, Argenti, C, Astuti, G, Bacaro, G, Bacchetta, G, Bagella, S, Banfi, E, Barberis, D, Bartolucci, F, Bernardo, L, Bonari, G, Brundu, G, Buccomino, G, Calvia, G, Cancellieri, L, Capuano, A, Celesti-Grapow, L, Conti, F, Cuena-Lombraña, A, D’Amico, F, De Fine, G, de Simone, L, Guacchio, E, Emili, F, Fanfarillo, E, Fascetti, S, Fiaschi, T, Fois, M, Fortini, P, Gentili, R, Giardini, M, Hussain, A, Iamonico, D, Laface, V, Lallai, A, Lazzaro, L, Lecis, A, Ligato, E, Loi, G, Lonati, M, Lozano, V, Maccherini, S, Mainetti, A, Mascia, F, Mei, G, Menini, F, Merli, M, Montesano, A, Mugnai, M, Musarella, C, Nota, G, Olivieri, N, Passalacqua, N, Pinzani, L, Pisano, A, Pittarello, M, Podda, L, Posillipo, G, Potenza, G, Probo, M, Prosser, F, Quaglini, L, Enri, S, Rivieccio, G, Roma-Marzio, F, Rosati, L, Selvaggi, A, Soldano, A, Stinca, A, Tasinazzo, S, Tassone, S, Terzi, M, Vallariello, R, Vangelisti, R, Verloove, F, Lastrucci, L, Galasso G., Domina G., Andreatta S., Argenti C., Astuti G., Bacaro G., Bacchetta G., Bagella S., Banfi E., Barberis D., Bartolucci F., Bernardo L., Bonari G., Brundu G., Buccomino G., Calvia G., Cancellieri L., Capuano A., Celesti-Grapow L., Conti F., Cuena-Lombraña A., D’Amico F. S., De Fine G., de Simone L., Guacchio E. D., Emili F., Fanfarillo E., Fascetti S., Fiaschi T., Fois M., Fortini P., Gentili R., Giardini M., Hussain A. N., Iamonico D., Laface V. L. A., Lallai A., Lazzaro L., Lecis A. P., Ligato E., Loi G., Lonati M., Lozano V., Maccherini S., Mainetti A., Mascia F., Mei G., Menini F., Merli M., Montesano A., Mugnai M., Musarella C. M., Nota G., Olivieri N., Passalacqua N. G., Pinzani L., Pisano A., Pittarello M., Podda L., Posillipo G., Potenza G., Probo M., Prosser F., Quaglini L. A., Enri S. R., Rivieccio G., Roma-Marzio F., Rosati L., Selvaggi A., Soldano A., Stinca A., Tasinazzo S., Tassone S., Terzi M., Vallariello R., Vangelisti R., Verloove F., and Lastrucci L.

Abstract

In this contribution, new data concerning the distribution of vascular flora alien to Italy are presented. It includes new records, confirmations, and status changes for Italy or for Italian administrative regions. Nomenclatural and distribution updates, published elsewhere, and corrections are provided as Suppl. material 1. © Gabriele Galasso et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Published
2022

3. Notulae to the Italian alien vascular flora: 9

Author

Galasso, G, Domina, G, Adorni, M, Angiolini, C, Apruzzese, M, Ardenghi, N, Assini, S, Aversa, M, Bacchetta, G, Banfi, E, Barberis, G, Bartolucci, F, Bernardo, L, Bertolli, A, Bonali, F, Bonari, G, Bonini, I, Bracco, F, Brundu, G, Buccomino, G, Buono, S, Calvia, G, Cambria, S, Castagnini, P, Ceschin, S, Dagnino, D, Di Gristina, E, Di Turi, A, Fascetti, S, Ferretti, G, Fois, M, Gentili, R, Gheza, G, Gubellini, L, Hofmann, N, Iamonico, D, Ilari, A, Kiraly, A, Kiraly, G, Laface, V, Lallai, A, Lazzaro, L, Lonati, M, Longo, D, Lozano, V, Lupoletti, J, Magrini, S, Mainetti, A, Manca, M, Marchetti, D, Mariani, F, Mariotti, M, Masin, R, Mei, G, Menini, F, Merli, M, Milani, A, Minuto, L, Mugnai, M, Musarella, C, Olivieri, N, Onnis, L, Passalacqua, N, Peccenini, S, Peruzzi, L, Pica, A, Pinzani, L, Pittarello, M, Podda, L, Prosser, F, Enri, S, Roma-Marzio, F, Rosati, L, Sarigu, M, Scafidi, F, Sciandrello, S, Selvaggi, A, Spampinato, G, Stinca, A, Tavilla, G, Toffolo, C, Tomasi, G, Turcato, C, Villano, C, Nepi, C, Galasso G., Domina G., Adorni M., Angiolini C., Apruzzese M., Ardenghi N. M. G., Assini S., Aversa M., Bacchetta G., Banfi E., Barberis G., Bartolucci F., Bernardo L., Bertolli A., Bonali F., Bonari G., Bonini I., Bracco F., Brundu G., Buccomino G., Buono S., Calvia G., Cambria S., Castagnini P., Ceschin S., Dagnino D., Di Gristina E., Di Turi A., Fascetti S., Ferretti G., Fois M., Gentili R., Gheza G., Gubellini L., Hofmann N., Iamonico D., Ilari A., Kiraly A., Kiraly G., Laface V. L. A., Lallai A., Lazzaro L., Lonati M., Longo D., Lozano V., Lupoletti J., Magrini S., Mainetti A., Manca M., Marchetti D., Mariani F., Mariotti M. G., Masin R. R., Mei G., Menini F., Merli M., Milani A., Minuto L., Mugnai M., Musarella C. M., Olivieri N., Onnis L., Passalacqua N. G., Peccenini S., Peruzzi L., Pica A., Pinzani L., Pittarello M., Podda L., Prosser F., Enri S. R., Roma-Marzio F., Rosati L., Sarigu M., Scafidi F., Sciandrello S., Selvaggi A., Spampinato G., Stinca A., Tavilla G., Toffolo C., Tomasi G., Turcato C., Villano C., Nepi C., Galasso, G, Domina, G, Adorni, M, Angiolini, C, Apruzzese, M, Ardenghi, N, Assini, S, Aversa, M, Bacchetta, G, Banfi, E, Barberis, G, Bartolucci, F, Bernardo, L, Bertolli, A, Bonali, F, Bonari, G, Bonini, I, Bracco, F, Brundu, G, Buccomino, G, Buono, S, Calvia, G, Cambria, S, Castagnini, P, Ceschin, S, Dagnino, D, Di Gristina, E, Di Turi, A, Fascetti, S, Ferretti, G, Fois, M, Gentili, R, Gheza, G, Gubellini, L, Hofmann, N, Iamonico, D, Ilari, A, Kiraly, A, Kiraly, G, Laface, V, Lallai, A, Lazzaro, L, Lonati, M, Longo, D, Lozano, V, Lupoletti, J, Magrini, S, Mainetti, A, Manca, M, Marchetti, D, Mariani, F, Mariotti, M, Masin, R, Mei, G, Menini, F, Merli, M, Milani, A, Minuto, L, Mugnai, M, Musarella, C, Olivieri, N, Onnis, L, Passalacqua, N, Peccenini, S, Peruzzi, L, Pica, A, Pinzani, L, Pittarello, M, Podda, L, Prosser, F, Enri, S, Roma-Marzio, F, Rosati, L, Sarigu, M, Scafidi, F, Sciandrello, S, Selvaggi, A, Spampinato, G, Stinca, A, Tavilla, G, Toffolo, C, Tomasi, G, Turcato, C, Villano, C, Nepi, C, Galasso G., Domina G., Adorni M., Angiolini C., Apruzzese M., Ardenghi N. M. G., Assini S., Aversa M., Bacchetta G., Banfi E., Barberis G., Bartolucci F., Bernardo L., Bertolli A., Bonali F., Bonari G., Bonini I., Bracco F., Brundu G., Buccomino G., Buono S., Calvia G., Cambria S., Castagnini P., Ceschin S., Dagnino D., Di Gristina E., Di Turi A., Fascetti S., Ferretti G., Fois M., Gentili R., Gheza G., Gubellini L., Hofmann N., Iamonico D., Ilari A., Kiraly A., Kiraly G., Laface V. L. A., Lallai A., Lazzaro L., Lonati M., Longo D., Lozano V., Lupoletti J., Magrini S., Mainetti A., Manca M., Marchetti D., Mariani F., Mariotti M. G., Masin R. R., Mei G., Menini F., Merli M., Milani A., Minuto L., Mugnai M., Musarella C. M., Olivieri N., Onnis L., Passalacqua N. G., Peccenini S., Peruzzi L., Pica A., Pinzani L., Pittarello M., Podda L., Prosser F., Enri S. R., Roma-Marzio F., Rosati L., Sarigu M., Scafidi F., Sciandrello S., Selvaggi A., Spampinato G., Stinca A., Tavilla G., Toffolo C., Tomasi G., Turcato C., Villano C., and Nepi C.

Abstract

In this contribution, new data concerning the distribution of vascular flora alien to Italy are presented. It includes new records, confirmations, exclusions, and status changes for Italy or for Italian administrative regions. Furthermore, three new combinations are proposed. Nomenclatural and distribution updates published elsewhere are provided as Suppl. material 1.

Published
2020

8. Notulae to the Italian alien vascular flora: 8

Author

Galasso, G, Domina, G, Andreatta, S, Angiolini, C, Ardenghi, N, Aristarchi, C, Arnoul, M, Azzella, M, Bacchetta, G, Bartolucci, F, Bodino, S, Bommartini, G, Bonari, G, Buono, S, Buono, V, Caldarella, O, Calvia, G, Corti, E, D'Antraccoli, M, De Luca, R, De Mattia, F, Di Natale, S, Di Turi, A, Esposito, A, Ferretti, G, Fiaschi, T, Fogu, M, Forte, L, Frigerio, J, Gubellini, L, Guzzetti, L, Hofmann, N, Laface, V, Laghetti, G, Lallai, A, La Rosa, A, Lazzaro, L, Lodetti, S, Lonati, M, Luchino, F, Magrini, S, Mainetti, A, Marignani, M, Maruca, G, Medagli, P, Mei, G, Menini, F, Mezzasalma, V, Misuri, A, Mossini, S, Mugnai, M, Musarella, C, Nota, G, Olivieri, N, Padula, A, Pascale, M, Pasquini, F, Peruzzi, L, Picella, G, Pinzani, L, Pirani, S, Pittarello, M, Podda, L, Enri, S, Rifici, C, Roma-Marzio, F, Romano, R, Rosati, L, Scafidi, F, Scarici, E, Scarici, M, Spampinato, G, Stinca, A, Wagensommer, R, Zanoni, G, Nepi, C, Galasso, Gabriele, Domina, Gianniantonio, Andreatta, Sebastiano, Angiolini, Claudia, Ardenghi, Nicola M. G., Aristarchi, Claudio, Arnoul, Matteo, Azzella, Mattia M., Bacchetta, Gianluigi, Bartolucci, Fabrizio, Bodino, Silvia, Bommartini, Giacomo, Bonari, Gianmaria, Buono, Sergio, Buono, Vito, Caldarella, Orazio, Calvia, Giacomo, Corti, Emilio, D'Antraccoli, Marco, De Luca, Rocco, De Mattia, Fabrizio, Di Natale, Stefano, Di Turi, Alessandra, Esposito, Assunta, Ferretti, Giulio, Fiaschi, Tiberio, Fogu, Maria C., Forte, Luigi, Frigerio, Jessica, Gubellini, Leonardo, Guzzetti, Lorenzo, Hofmann, Nicole, Laface, Valentina L. A., Laghetti, Gaetano, Lallai, Andrea, La Rosa, Alfonso, Lazzaro, Lorenzo, Lodetti, Silvano, Lonati, Michele, Luchino, Fabio, Magrini, Sara, Mainetti, Andrea, Marignani, Michela, Maruca, Gina, Medagli, Pietro, Mei, Giacomo, Menini, Flavio, Mezzasalma, Valerio, Misuri, Alice, Mossini, Sara, Mugnai, Michele, Musarella, Carmelo M., Nota, Ginevra, Olivieri, Nicola, Padula, Alessia, Pascale, Marziano, Pasquini, Federico, Peruzzi, Lorenzo, Picella, Gianni, Pinzani, Lorenzo, Pirani, Silvia, Pittarello, Marco, Podda, Lina, Enri, Simone Ravetto, Rifici, Carmelo D., Roma-Marzio, Francesco, Romano, Rosario, Rosati, Leonardo, Scafidi, Filippo, Scarici, Enrico, Scarici, Marco, Spampinato, Giovanni, Stinca, Adriano, Wagensommer, Robert P., Zanoni, Giovanni, Nepi, Chiara, Galasso, G, Domina, G, Andreatta, S, Angiolini, C, Ardenghi, N, Aristarchi, C, Arnoul, M, Azzella, M, Bacchetta, G, Bartolucci, F, Bodino, S, Bommartini, G, Bonari, G, Buono, S, Buono, V, Caldarella, O, Calvia, G, Corti, E, D'Antraccoli, M, De Luca, R, De Mattia, F, Di Natale, S, Di Turi, A, Esposito, A, Ferretti, G, Fiaschi, T, Fogu, M, Forte, L, Frigerio, J, Gubellini, L, Guzzetti, L, Hofmann, N, Laface, V, Laghetti, G, Lallai, A, La Rosa, A, Lazzaro, L, Lodetti, S, Lonati, M, Luchino, F, Magrini, S, Mainetti, A, Marignani, M, Maruca, G, Medagli, P, Mei, G, Menini, F, Mezzasalma, V, Misuri, A, Mossini, S, Mugnai, M, Musarella, C, Nota, G, Olivieri, N, Padula, A, Pascale, M, Pasquini, F, Peruzzi, L, Picella, G, Pinzani, L, Pirani, S, Pittarello, M, Podda, L, Enri, S, Rifici, C, Roma-Marzio, F, Romano, R, Rosati, L, Scafidi, F, Scarici, E, Scarici, M, Spampinato, G, Stinca, A, Wagensommer, R, Zanoni, G, Nepi, C, Galasso, Gabriele, Domina, Gianniantonio, Andreatta, Sebastiano, Angiolini, Claudia, Ardenghi, Nicola M. G., Aristarchi, Claudio, Arnoul, Matteo, Azzella, Mattia M., Bacchetta, Gianluigi, Bartolucci, Fabrizio, Bodino, Silvia, Bommartini, Giacomo, Bonari, Gianmaria, Buono, Sergio, Buono, Vito, Caldarella, Orazio, Calvia, Giacomo, Corti, Emilio, D'Antraccoli, Marco, De Luca, Rocco, De Mattia, Fabrizio, Di Natale, Stefano, Di Turi, Alessandra, Esposito, Assunta, Ferretti, Giulio, Fiaschi, Tiberio, Fogu, Maria C., Forte, Luigi, Frigerio, Jessica, Gubellini, Leonardo, Guzzetti, Lorenzo, Hofmann, Nicole, Laface, Valentina L. A., Laghetti, Gaetano, Lallai, Andrea, La Rosa, Alfonso, Lazzaro, Lorenzo, Lodetti, Silvano, Lonati, Michele, Luchino, Fabio, Magrini, Sara, Mainetti, Andrea, Marignani, Michela, Maruca, Gina, Medagli, Pietro, Mei, Giacomo, Menini, Flavio, Mezzasalma, Valerio, Misuri, Alice, Mossini, Sara, Mugnai, Michele, Musarella, Carmelo M., Nota, Ginevra, Olivieri, Nicola, Padula, Alessia, Pascale, Marziano, Pasquini, Federico, Peruzzi, Lorenzo, Picella, Gianni, Pinzani, Lorenzo, Pirani, Silvia, Pittarello, Marco, Podda, Lina, Enri, Simone Ravetto, Rifici, Carmelo D., Roma-Marzio, Francesco, Romano, Rosario, Rosati, Leonardo, Scafidi, Filippo, Scarici, Enrico, Scarici, Marco, Spampinato, Giovanni, Stinca, Adriano, Wagensommer, Robert P., Zanoni, Giovanni, and Nepi, Chiara

Abstract

In this contribution, new data concerning the distribution of vascular flora alien to Italy are presented. It includes new records, confirmations, exclusions, and status changes for Italy or for Italian administrative regions of taxa in the genera Bunias, Calocedrus, Calycanthus, Celosia, Clerodendrum, Convolvulus, Crassula, Cyclamen, Datura, Dicliptera, Eragrostis, Erigeron, Gamochaeta, Gazania, Impatiens, Kolkwitzia, Leucaena, Ludwigia, Medicago, Muscari, Nigella, Oenothera, Opuntia, Paulownia, Petroselinum, Phyllostachys, Physalis, Pseudosasa, Quercus, Reynoutria, Roldana, Saccharum, Sedum, Semiarundinaria, Senecio, Sisyrinchium, Solanum, Sporobolus, Tulipa, Vachellia, Verbena, and Youngia. Nomenclatural and distribution updates published elsewhere are provided as Suppl. material 1.

Published
2019

10. Experience in using a new primer for CVC priming in hemodialysis treatment

Author

Borin, D., Piovan, C., Bovolon, T., Olivieri, N., Barbiero, M., Loschiavo, C., Borin, D., Piovan, C., Bovolon, T., Olivieri, N., Barbiero, M., and Loschiavo, C.

Abstract

No abstract, Il catetere venoso centrale rappresenta uno dei possibili accessi vascolari per il paziente in emodialisi. I protocolli attualmente in uso per la procedura di attacco prevedono una serie di manovre di movimentazione del sangue seguite da ripetute connessioni-sconnessioni di alcune siringhe, con possibili rischi infettivi sia per il paziente sia per l'ambiente e con una valutazione soggettiva della portata dell'accesso. In questa breve esperienza abbiamo utilizzato un nuovo presidio, denominato “Haemocatch”, che permette di aspirare il sangue da entrambi i lumi del catetere venoso centrale mediante una sola siringa, di restituire il sangue filtrato e privo di eventuali coaguli e di quantificare la portata dell'accesso prima dell'inizio della seduta dialitica in un sistema chiuso. I vantaggi di questo device innovativo sono la standardizzazione del metodo di priming, la riduzione del numero delle connessioni con conseguente minor esposizione al rischio di infezioni, la maggiore sicurezza sia per il paziente sia per l'operatore e la preliminare valutazione della portata dell'accesso, che fornisce un'importante informazione all'operatore e riduce l'evenienza di interruzione del trattamento per portata insufficiente.

Published
2018

13. Deferoxamine in Thalassemia Major

Author

Splendiani, G., Tozzo, C., Mazzarella, V., Casciani, C. U., Lucarelli, G., Angelucci, E., Clift, R., Cazzola, M., Locatelli, F., de Stefano, P., Olivieri, N. F., Nathan, D. G., and Cohen, A. R.

Subjects
medicine.medical_specialty, Blood transfusion, business.industry, Thalassemia, medicine.medical_treatment, MEDLINE, Beta thalassemia, General Medicine, Hemosiderosis, medicine.disease, Diabetic foot, Deferoxamine, Internal medicine, medicine, Foot ulcers, business, medicine.drug
Published
1995
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15. The risks and benefits of long-term use of hydroxyurea in sickle cell anemia: A 17.5 year follow-up

Author

Bridges, K., Telfer, M., Ataga, Kenneth, Orringer, E., Hoehner, C., Hernandez, S., Valdez, S., Temple, D., Shurin, S., Johnson-Telfair, A., Hagar, W., Vichinsky, E., Smith, Wally, Steinberg, Martin H., Kleman, K., Rosse, W., Waller, L., Barber, Y., Chow, J., Gascon, P., Winograd, C., Di Paolo, P., Hui, M., Moshang, J., Olivieri, N., Dorn, L., Siteman, J., Embury, S., Eckman, J., Ballas, Samir K., Anderson, A., White, L., Harrington, T., Talischy-Zahed, N., Shaw, D., Scott, B., Waclawiw, Myron A., Labrousse, W., Adler, B., Phillips, G., Bigelow, C., Armstrong, F. Danny, Chiarucci, K., Childerie, S., McLaughlin, K., Mandell, E., DeCastro, Laura, Claster, S., Knors, V., Gargiulo, S., Jones, S., Tynan, B., Saunthararajah, Y., Saunders, T., Maddox, B., Hackney-Stevens, E., Keverline, L., Gardner, D., Carter-Randall, E., Schmidt, B., Tracy, A., Davies, D., Carlos, T., Kutlar, Abdullah, Finke, H., Nwokolo, C., Perlin, E., Onyekwere, O. C., Okam, M., Peace, D., Milner, P., Koshy, M., Sheikhai, M., Daitch, L., Swerdlow, Paul, Pendarvis, G., Harrell, R., Case, E., Brenner, A., Bailey, J. H., Strayhorn, D., Prchal, J., Ramirez, G., Dosik, H., Platt, A., McGee, M., Lewis, N., Castro, Oswaldo, Palmer, A., Wilkes, E., Braddock, J., Sabahi, V., Pegelow, C., Bellevue, R., McArdle, T., O'Brien, R., Williams, K., Usry, L., Eskridge, L., Berman, B., Allen, G. E., Earles, A., Bryan, M., Davis, A., Rodriguez, E. M., Souffrant, H., Genther, K., McCarthy, William F., Roundtree-Schmotzer, A., and Ryans, P.

Abstract

A randomized, controlled clinical trial established the efficacy and safety of short-term use of hydroxyurea in adult sickle cell anemia. To examine the risks and benefits of long-term hydroxyurea usage, patients in this trial were followed for 17.5 years during which they could start or stop hydroxyurea. The purpose of this follow-up was to search for adverse outcomes and estimate mortality. For each outcome and for mortality, exact 95% confidence intervals were calculated, or tests were conducted at α = 0.05 level (p-value

Published
2010
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16. A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with beta-thalassemia

Author

Cappellini, MD Cohen, A Piga, A Bejaoui, M Perrone, S and Agaoglu, L Aydinok, Y Kattamis, A Kilinc, Y Porter, J Capra, M Galanello, R Fattoum, S Drelichman, G and Magnano, C Verissimo, M Athanassiou-Metaxa, M Giardina, P and Kourakli-Symeonidis, A Janka-Schaub, G Coates, T and Vermylen, C Olivieri, N Thuret, I Opitz, H and Ressayre-Djaffer, C Marks, P Alberti, D

Abstract

Deferasirox (ICL670) is a once-daily oral iron chelator developed for the treatment of chronic iron overload from blood transfusions. A comparative phase 3 trial was conducted to demonstrate the efficacy of deferasirox in regularly transfused patients with beta-thalassemia aged 2 years or older. Patients were randomized and received treatment with deferasirox (n = 296) or deferoxamine (n = 290), with dosing of each according to baseline liver iron concentration (LIC). The primary endpoint was maintenance or reduction of LIC; secondary endpoints included safety and tolerability, change in serum ferritin level, and net body iron balance. In both arms, patients with LIC values of 7 mg Fe/g dry weight (dw) or higher had significant and similar dose-dependent reductions in LIC and serum ferritin, and effects on net body iron balance. However, the primary endpoint was not met in the overall population, possibly due to the fact that proportionally lower doses of deferasirox relative to deferoxamine were administered to patients with LIC values less than 7 mg Fe/g dw. The most common adverse events included rash, gastrointestinal disturbances, and mild nonprogressive increases in serum creatinine. No agranulocytosis, arthropathy, or growth failure was associated with deferasirox administration. Deferasirox is a promising once-daily oral therapy for the treatment of transfusional iron overload.

Published
2006

17. Thalassaemia in Sri Lanka: implications for the future health burden of Asian populations. Sri Lanka Thalassaemia Study Group

Author

de Silva, S, Fisher, C, Premawardhena, A, Lamabadusuriya, S, Peto, T, Perera, G, Old, J, Clegg, J, Olivieri, N, and Weatherall, D

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, hemic and lymphatic diseases
Abstract

BACKGROUND: Thalassaemias pose an increasing problem for the Indian subcontinent and many Asian countries. We analysed the different types of thalassaemia in the Sri Lankan population, surveyed gene frequencies in schoolchildren, and estimated the burden of disease and requirements for its control. METHODS: We analysed blood samples from patients attending clinics in nine hospitals and defined the different types of beta thalassaemia by high-performance liquid chromatography (HPLC) and DNA analysis. The range of mutations was obtained by analysis of beta-globin genes. Capillary blood was obtained from schoolchildren from different parts of the island and analysed by HPLC to provide an approximate assessment of the carrier frequency of beta thalassaemia and haemoglobin E (HbE). To estimate the frequency of alpha thalassaemia the alpha-globin genotypes were also analysed when it was possible. FINDINGS: Blood samples were obtained from 703 patients with beta thalassaemia and from 1600 schoolchildren. The thalassaemia mutations were unevenly spread. Although 23 different beta-thalassaemia mutations were found, three accounted for the thalassaemia phenotype in about 70% of the patients, most whom are homozygotes or compound heterozygotes for IVS1-5 (G-->C) or IVS1-1 (G-->A). The third common mutation, codon 26 (G-->A), which produces HbE, interacts with one or other of these mutations to produce HbE/beta thalassaemia; this comprises 13.0-30.9% of cases in the main centres. Samples from 472 patients were analysed to determine the alpha-globin genotype. Overall, 15.5% patients were carriers for deletion forms of alpha+ thalassaemia. Average gene frequencies showed that there will be more than 2000 patients requiring treatment at any one time, in the future, of whom those with HbE/beta thalassaemia will account for about 40%. INTERPRETATION: In Sri Lanka, interactions of the two common beta-thalassaemia alleles will nearly always result in a transfusion-dependent disorder. However, about 40% of patients will have HbE/beta thalassaemia, which has a variable course. The management of these disorders could require about 5% of the total health budget. We need to learn more about the natural history and appropriate management of HbE/beta thalassaemia if resources are to be used effectively.

Published
2000

18. The risks and benefits of long-term use of hydroxyurea in sickle cell anemia: A 17.5 year follow-up.

Author

Steinberg, M. H., McCarthy, W. F., Castro, O., Ballas, S. K., Armstrong, F. D., Smith, W., Ataga, K., Swerdlow, P., Kutlar, A., DeCastro, L., Waclawiw, M. A., Orringer, E., Jones, S., Strayhorn, D., Rosse, W., Phillips, G., Pearce, D., Johnson-Telfair, A., Daitch, L., Milner, P., Tracy, A., Valdez, S., Allen, G. E., Moshang, J., Scott, B., Bigelow, C., Anderson, A., Sabahi, V., Harrington, T., Labrousse, W., Pegelow, C., Temple, D., Case, E., Harrell, R., Childerie, S., Embury, S., Schmidt, B., Davies, D., Saunthararajah, Y., Koshy, M., Talischy-Zahed, N., Dorn, L., Pendarvis, G., McGee, M., Telfer, M., Davis, A., Onyekwere, O. C., Nwokolo, C., Finke, H., Perlin, E., Siteman, J., Bryan, M., Saunders, T., Barber, Y., Gascon, P., Di Paolo, P., Gargiulo, S., Eckman, J., Carter-Randall, E., Bailey, J. H., Platt, A., Waller, L., Ramirez, G., Knors, V., Hernandez, S., Rodriguez, E. M., Wilkes, E., Vichinsky, E., Hagar, W., Hoehner, C., Hackney-Stevens, E., Claster, S., Earles, A., Kleman, K., McLaughlin, K., White, L., Maddox, B., Usry, L., Brenner, A., Williams, K., O'Brien, R., Genther, K., Shurin, S., Berman, B., Chiarucci, K., Keverline, L., Olivieri, N., Chow, J., Hui, M., Shaw, D., Lewis, N., Okam, M., Mandell, E., Palmer, A., Bridges, K., Tynan, B., Winograd, C., Bellevue, R., Dosik, H., Sheikhai, M., Ryans, P., Souffrant, H., Adler, B., Eskridge, L., Prchal, J., Braddock, J., McArdle, T., Carlos, T., Roundtree-Schmotzer, A., Gardner, D., Steinberg, M. H., McCarthy, W. F., Castro, O., Ballas, S. K., Armstrong, F. D., Smith, W., Ataga, K., Swerdlow, P., Kutlar, A., DeCastro, L., Waclawiw, M. A., Orringer, E., Jones, S., Strayhorn, D., Rosse, W., Phillips, G., Pearce, D., Johnson-Telfair, A., Daitch, L., Milner, P., Tracy, A., Valdez, S., Allen, G. E., Moshang, J., Scott, B., Bigelow, C., Anderson, A., Sabahi, V., Harrington, T., Labrousse, W., Pegelow, C., Temple, D., Case, E., Harrell, R., Childerie, S., Embury, S., Schmidt, B., Davies, D., Saunthararajah, Y., Koshy, M., Talischy-Zahed, N., Dorn, L., Pendarvis, G., McGee, M., Telfer, M., Davis, A., Onyekwere, O. C., Nwokolo, C., Finke, H., Perlin, E., Siteman, J., Bryan, M., Saunders, T., Barber, Y., Gascon, P., Di Paolo, P., Gargiulo, S., Eckman, J., Carter-Randall, E., Bailey, J. H., Platt, A., Waller, L., Ramirez, G., Knors, V., Hernandez, S., Rodriguez, E. M., Wilkes, E., Vichinsky, E., Hagar, W., Hoehner, C., Hackney-Stevens, E., Claster, S., Earles, A., Kleman, K., McLaughlin, K., White, L., Maddox, B., Usry, L., Brenner, A., Williams, K., O'Brien, R., Genther, K., Shurin, S., Berman, B., Chiarucci, K., Keverline, L., Olivieri, N., Chow, J., Hui, M., Shaw, D., Lewis, N., Okam, M., Mandell, E., Palmer, A., Bridges, K., Tynan, B., Winograd, C., Bellevue, R., Dosik, H., Sheikhai, M., Ryans, P., Souffrant, H., Adler, B., Eskridge, L., Prchal, J., Braddock, J., McArdle, T., Carlos, T., Roundtree-Schmotzer, A., and Gardner, D.

Abstract

A randomized, controlled clinical trial established the efficacy and safety of short-term use of hydroxyurea in adult sickle cell anemia. To examine the risks and benefits of long-term hydroxyurea usage, patients in this trial were followed for 17.5 years during which they could start or stop hydroxyurea. The purpose of this follow-up was to search for adverse outcomes and estimate mortality. For each outcome and for mortality, exact 95% confidence intervals were calculated, or tests were conducted at alpha = 0.05 level (P-value <0.05 for statistical significance). Although the death rate in the overall study cohort was high (43.1%; 4.4 per 100 person-years), mortality was reduced in individuals with long-term exposure to hydroxyurea. Survival curves demonstrated a significant reduction in deaths with long-term exposure. Twenty-four percent of deaths were due to pulmonary complications; 87.1% occurred in patients who never took hydroxyurea or took it for <5 years. Stroke, organ dysfunction, infection, and malignancy were similar in all groups. Our results, while no longer the product of a randomized study because of the ethical concerns of withholding an efficacious treatment, suggest that long-term use of hydroxyurea is safe and might decrease mortality.

Published
2010

25. Mutations in the erythropoietin receptor gene are not a common cause of Diamond-Blackfan anemia

Author

Dianzani, I, Garelli, E, Dompè, C, Crescenzio, N, Locatelli, Franco, Schilirò, G, Castaman, G, Bagnara, G P, Olivieri, N F, Gabutti, V, Ramenghi, U, Locatelli, F (ORCID:0000-0002-7976-3654), Dianzani, I, Garelli, E, Dompè, C, Crescenzio, N, Locatelli, Franco, Schilirò, G, Castaman, G, Bagnara, G P, Olivieri, N F, Gabutti, V, Ramenghi, U, and Locatelli, F (ORCID:0000-0002-7976-3654)

Abstract

Diamond-Blackfan anemia (DBA) is an inherited pure red blood cell aplasia that often requires lifelong transfusional support. The origin of the imperfect erythrogenesis is not known. The existence of more than one molecular basis for DBA is indicated by its different modes of inheritance and widely variable clinical phenotypes. Several erythroid growth factors have been thought to have a role in the pathogenesis of DBA. However, there is neither molecular nor clinical evidence for the involvement of stem cell factor or interleukin-3. The observation of elevated erythropoietin (EPO) concentrations and an impaired in vivo and in vitro response to pharmacologic doses of recombinant human EPO has suggested a defective EPO function in the pathogenesis of DBA. We have investigated the possible involvement of the EPO receptor (EPO-R) gene in 23 patients by screening its coding sequence for mutations using single-strand conformation polymorphism (SSCP). A Southern blot and hybridization with an EPO-R probe was also performed on DNA from seven patients. No causal mutations were identified. The absence of concordant segregation of the disease with the EPO-R gene in two informative families ruled out its role in their DBA children. These findings demonstrate that DBA is not commonly associated with EPO-R gene mutations.

Published
1996

26. IDENTIFICATION OF MICRODELETIONS SPANNING THE DIAMOND-BLACKFAN ANEMIA (DBA) LOCUS ON 19Q13 AND EVIDENCE FOR GENETIC HETEROGENEITY

Author

Gustavsson, P, primary, Garelli, E, additional, Draptchinskaia, N, additional, Ball, S, additional, Willing, T N, additional, Tentler, D, additional, Dianzani, I, additional, Punnett, H H, additional, Shafer, F E, additional, Cario, H, additional, Ramenghi, U, additional, Glomstein, A, additional, Pfeiffer, R A, additional, Goringe, A, additional, Olivieri, N F, additional, Smibert, E, additional, Tchernia, G, additional, Elinder, G, additional, and Dahl, N, additional

Published
1999
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35. Experimental verocytotoxemia in rabbits

Author

Richardson, S E, primary, Rotman, T A, additional, Jay, V, additional, Smith, C R, additional, Becker, L E, additional, Petric, M, additional, Olivieri, N F, additional, and Karmali, M A, additional

Published
1992
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41. Prospective RBC phenotype matching in a stroke-prevention trial in sickle cell anemia: a multicenter transfusion trial.

Author

Vichinsky, E.P., Luban, N.L.C., Wright, E., Olivieri, N., Driscoll, C., Pegelow, C.H., Adams, R.J., Luban, N L, and Stroke Prevention Trail in Sickle Cell Anemia

Subjects
AUTOANTIBODY analysis, SICKLE cell anemia treatment, STROKE prevention, IMMUNOGLOBULIN analysis, ERYTHROCYTES, BLOOD transfusion, BLOOD transfusion reaction, CLINICAL trials, COMPARATIVE studies, LONGITUDINAL method, RESEARCH methodology, MEDICAL cooperation, RESEARCH, SICKLE cell anemia, PHENOTYPES, EVALUATION research, RANDOMIZED controlled trials, BLOOD grouping & crossmatching
Abstract

Background: Most sickle cell anemia patients undergo transfusion therapy to prevent complications. The Stroke Prevention Trial in Sickle Cell Anemia showed that transfusion therapy is effective in the primary prevention of stroke. Despite its efficacy, transfusion therapy is limited by alloimmunization. The purpose of this study was to determine if a multicenter trial could implement a transfusion program utilizing phenotypically matched blood to reduce alloimmunization.Study Design and Methods: One hundred thirty children underwent RBC phenotyping and antibody screening with review of blood bank records. The protocol required use of WBC-reduced RBCs, which were matched for E, C, and Kell. Monthly alloantibody testing and review of transfusion forms were performed to determine compliance and the occurrence of any adverse events.Results: Patient RBCs expressed a low frequency of Kell (2%), E (20%), and C (25%) antigens. Sixty-one patients received 1830 units. Ninety-seven percent of all units were WBC reduced. Only 29 units were inadvertently not matched for E, C, and Kell. Five patients (8%) developed a clinically significant alloantibody. Four developed a single antibody to E or Kell. Three patients (5%) developed a warm autoantibody. There were 11 transfusion reactions and 8 transfusion-associated events. Transfusion reactions included 6 febrile reactions (0.33%/unit), 3 allergic (0.16%/unit), and 2 hemolytic (0.11%/unit). Associated events included 4 episodes of hypertension (0.22%/unit), 3 crises (0.16%/unit), and 1 transient ischemic attack (0.05%/unit).Conclusion: This is the first multicenter study to show that extended RBC phenotyping can be implemented nationwide. Compared to studies, the alloimmunization rate dropped from 3 percent to 0.5 percent per unit, and hemolytic transfusion reactions dropped by 90 percent. It is recommended that all transfused sickle cell anemia patients be antigen matched for E, C, and Kell. Patients should be closely monitored during transfusions to avoid preventable risks. [ABSTRACT FROM AUTHOR]

Published
2001

43. Visual and auditory neurotoxicity in patients receiving subcutaneous deferoxamine infusions.

Author

Olivieri, N F, Buncic, J R, Chew, E, Gallant, T, Harrison, R V, Keenan, N, Logan, W, Mitchell, D, Ricci, G, and Skarf, B

Abstract

Of 89 patients receiving nightly subcutaneous deferoxamine for transfusion-dependent thalassemia major or Diamond-Blackfan anemia, 13 presented with visual loss or deafness of acute onset or both. Detailed ophthalmologic, audiologic, and evoked-potential studies uncovered abnormalities caused by neurotoxicity in 27 more. Four patients with visual loss had optic neuropathy, with a marked decrease in acuity, loss of color vision, and delayed visual evoked potentials. Five asymptomatic patients had changes in the pigment of the retinal epithelium. The hearing loss was characterized by a high-frequency sensorineural deficit, which necessitated hearing aids in six patients. When deferoxamine was stopped, recovery of vision was complete in 2 patients and partial in 2, and in 22 patients with abnormal audiograms, reversal of the hearing deficit was complete in 4 and partial in 1. An analysis of the clinical data showed that members of the affected group were younger, had lower serum ferritin values, and were self-administering higher doses of deferoxamine per kilogram of body weight. Significantly lower doses of deferoxamine were being taken by patients without abnormalities than by those with visual symptoms, abnormal audiograms, or prolonged evoked potentials (P less than 0.001, less than 0.006, and less than 0.04, respectively). The data implicate high-dose deferoxamine as a central factor in the pathogenesis of the neurotoxicity. We strongly recommend careful regulation of the deferoxamine dosage and serial audiovisual monitoring in all patients receiving the drug. [ABSTRACT FROM AUTHOR]

Published
1986
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49. Analysis of hemoglobin F production in Saudi Arabian families with sickle cell anemia

Author

Miller, BA, Salameh, M, Ahmed, M, Olivieri, N, Antognetti, G, Orkin, SH, Huisman, TH, and Nathan, DG

Abstract

Erythrocytes and progenitor-derived erythroblasts of sickle cell anemia patients from the Eastern Province of Saudi Arabia contain increased fetal hemoglobin and G gamma globin. A distinctive DNA polymorphism haplotype in the beta globin gene cluster (++- +-), tightly coupled to a C----T substitution at position -158 5' to the cap site of the G gamma globin gene, is strongly associated with sickle cell disease in this region. To determine whether the increased fetal hemoglobin production and/or elevated G gamma globin content are tightly linked to this haplotype, we studied 55 members of five Saudi families in which sickle cell disease is present. The results did not suggest a tight linkage of the haplotype to increased fetal hemoglobin production. On the other hand, several sickle trait family members heterozygous for the haplotype had normal fetal hemoglobin production in culture but elevated G gamma to A gamma ratios in peripheral blood. This observation suggests that in this genetic background increased expression of the G gamma globin gene may occur without a measurable increase in total fetal hemoglobin production. The family studies also clearly demonstrate that increased fetal hemoglobin production by erythroid progenitors is dependent on zygosity for the sickle gene in this population. These findings strongly suggest that other factors, such as the products of genes stimulated by hemolytic stress or other genetic determinants associated with the Saudi beta S chromosome, may interact with the -158 C----T substitution and influence gamma globin gene expression in this population.

Published
1987
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50. A HighPerformance Liquid Chromatographic Method for the Measurement of the Iron Chelator 12Dimethyl3hydroxypyridin4one in Human Plasma

Author

Klein, J., Damani, L. A., Chung, D., Epemoulu, O., Olivieri, N., and Koren, G.

Abstract

1,2-Dimethyl-3-hydroxypyridin-4-one (CP020 or L1) is a novel oral iron chelator that has proved to be effective in animals and humans. A rapid, accurate, and sensitive high-performance liquid chromatography method is described for measuring L1in human plasma using a Hypercarb 7 μm column and monitoring the column eluent by ultraviolet absorption at 280 nm. CP020 and the internal standard (CP094) were extracted into dichloromethane (2x5 ml) from plasma at neutral pH [0.25 ml of plasma + 0.75 ml of 60 m M3-(N-morpholino)propanesulfonic acid buffer, pH 7.4]. The method proved to be linear (r2= 0.998) in the clinical range of 0.5–50 μg/ml when 0.25 ml of plasma was used, with the coefficient of variation less than 10 even at the lower concentration range.

Published
1991

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