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5. Neurocognition and quality of life after reinitiating antiretroviral therapy in children randomized to planned treatment interruption

Author

Ananworanich, J, Melvin, D, Amador, Jt, Childs, T, Medin, G, Boscolo, V, Compagnucci, A, Kanjanavanit, S, Montero, S, Gibb, Dm, PENTA 11 Study Group including Aboulker, J, Babiker, A, Belfrage, E, Bernardi, S, Bologna, R, Burger, D, Butler, K, Castelli Gattinara, G, Castro, H, Clayden, P, Cressey, T, Darbyshire, Jh, Debré, M, de Groot, R, della Negra, M, di Biagio, A, De Rossi, A, Duicelescu, D, Faye, A, Giaquinto, C, Giacomet, V, Grosch Wörner, I, Hainault, M, Klein, N, Lallemant, M, Levy, J, Lyall, H, Marczynska, M, Marques, L, Mardarescu, M, Mellado Peña MJ, Nadal, D, Nastouli, E, Naver, L, Niehues, T, Peckham, C, Pillay, D, Popieska, J, Ramos Amador JT, Rojo Conejo, P, Rosado, L, Rosso, R, Rudin, C, Scherpbier, Hj, Sharland, M, Stevanovic, M, Thorne, C, Tovo, Pier Angelo, Tudor Williams, G, Turkova, A, Valerius, N, Volokha, A, Walker, As, Welch, S, Wintergerst, U, Aboulker, Jp, Burger, Dm, Green, H, Harper, L, Mofenson, L, Moye, J, Saïdi, Y, Cressey, Tr, Jacqz Aigrain, E, Khoo, S, Regazzi, M, Tréluyer, Jm, Ngo Giang Huong, N, Muñoz Fernandez MA, Hill, C, Lepage, P, Pozniak, A, Vella, S, Chêne, G, Vesikari, T, Hadjou, G, Léonardo, S, Riault, Y, Bleier, J, Buck, L, Duong, T, Farrelly, L, Forcat, S, Harrison, L, Horton, J, Johnson, D, Taylor, C, Chalermpantmetagul, S, Peongjakta, R, Khamjakkaew, W, Than in at, K, Chailert, S, Jourdain, G, Le Coeur, S, Floret, D, Costanzo, P, Le Thi TT, Monpoux, F, Mellul, S, Caranta, I, Boudjoudi, N, Firtion, G, Denon, M, Charlemaine, E, Picard, F, Hellier, E, Heuninck, C, Damond, F, Alexandre, G, Tricoire, J, Antras, M, Lachendowier, C, Nicot, F, Krivine, A, Rivaux, D, Notheis, G, Strotmann, G, Schlieben, S, Rampon, O, Zanchetta, M, Ginocchio, F, Viscoli, C, Martino, A, Pontrelli, G, Baldassar, S, Concato, C, Mazza, A, Rossetti, G, Dobosz, S, Oldakowska, A, Popielska, J, Kaflik, M, Stanczak, J, Stanczack, G, Dyda, T, Kruk, M, González Tomé MI, Delgado García, R, Fernandez Gonzalez MT, Mellado Peña, M, Martín Fontelos, P, Garcia Mellado MI, Medina, Af, Ascencion, B, Garcia Bermejo, I, Navarro Gomez DM, Saavedra, J, Prieto, C, Jimenez, Jl, Garcia Torre, A, de José Gómez MI, García Rodriguez MC, Moreno Pérez, D, Núñez Cuadros, E, Asensi Botet, F, Otero Reigada, C, Pérez Tamarit MD, Vilalta, R, Molina Moreno JM, Rainer, T, Schupbach, J, Rutishauser, M, Bunupuradah, T, Butterworth, O, Phasomsap, C, Prasitsuebsai, W, Chuanjaroen, T, Jupimai, T, Ubolyam, S, Phanuphak, P, Puthanakit, T, Pancharoen, C, Mai, C, Namwong, T, Punsakoon, W, Payakachat, S, Chutima, D, Raksasang, M, Foster, C, Hamadache, D, Campbell, S, Newbould, C, Monrose, C, Abdulla, A, Walley, A, Patel, D, Kaye, S, Seery, P, Rankin, A, Wildfire, A, Novelli, V, Shingadia, D, Moshal, K, Flynn, J, Clapson, M, Allen, A, Spencer, L, Rackstraw, C, Ward, B, Parkes, K, Depala, M, Jacobsen, M, Poulsom, H, Barkley, L, Miah, J, Lurie, P, Keane, C, Mcmaster, P, Phipps, M, Orendi, J, Farmer, C, Liebeschuetz, S, Sodeinde, O, Wong, S, Bostock, V, Heath, Y, Scott, S, Gandhi, K, Lewis, P, Daglish, J, Miles, K, Summerhill, L, Subramaniam, B, Weiner, L, Famiglietti, M, Rana, S, Yu, P, Roa, J, Puga, A, Haerry, A., AII - Amsterdam institute for Infection and Immunity, Paediatric Infectious Diseases / Rheumatology / Immunology, and Global Health

Subjects
0301 basic medicine, Male, Pediatrics, medicine.medical_specialty, antiretroviral therapy, children, HIV, neurocognition, neurodevelopment, quality of life, treatment interruption, Immunology and Allergy, Immunology, Infectious Diseases, Adolescent, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Antiretroviral Therapy, HIV Infections, Standard score, 03 medical and health sciences, 0302 clinical medicine, Cognition, Acquired immunodeficiency syndrome (AIDS), Antiretroviral Therapy, Highly Active, Memory span, Medicine, Humans, Highly Active, 030212 general & internal medicine, Child, Wechsler Intelligence Scale for Children, business.industry, Wechsler Adult Intelligence Scale, medicine.disease, 030112 virology, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Treatment Outcome, Anti-Retroviral Agents, Test score, Mann–Whitney U test, Quality of Life, Female, business, Neurocognitive
Abstract

Item does not contain fulltext OBJECTIVE: Understanding the effects of antiretroviral treatment (ART) interruption on neurocognition and quality of life (QoL) are important for managing unplanned interruptions and planned interruptions in HIV cure research. DESIGN: Children previously randomized to continuous (continuous ART, n = 41) vs. planned treatment interruption (PTI, n = 47) in the Pediatric European Network for Treatment of AIDS (PENTA) 11 study were enrolled. At study end, PTI children resumed ART. At 1 and 2 years following study end, children were assessed by the coding, symbol search and digit span subtests of Wechsler Intelligence Scale for Children (6-16 years old) or Wechsler Adult Intelligence Scale (>/=17 years old) and by Pediatrics QoL questionnaires for physical and psychological QoL. Transformed scaled scores for neurocognition and mean standardized scores for QoL were compared between arms by t-test and Mann-Whitney U test, respectively. Scores indicating clinical concern were compared (

Published
2016

6. Whole-Genome Sequencing Reveals the Contribution of Long-Term Carriers in Staphylococcus aureus Outbreak Investigation

Author

Gordon, N. C., primary, Pichon, B., additional, Golubchik, T., additional, Wilson, D. J., additional, Paul, J., additional, Blanc, D. S., additional, Cole, K., additional, Collins, J., additional, Cortes, N., additional, Cubbon, M., additional, Gould, F. K., additional, Jenks, P. J., additional, Llewelyn, M., additional, Nash, J. Q., additional, Orendi, J. M., additional, Paranthaman, K., additional, Price, J. R., additional, Senn, L., additional, Thomas, H. L., additional, Wyllie, S., additional, Crook, D. W., additional, Peto, T. E. A., additional, Walker, A. S., additional, and Kearns, A. M., additional

Published
2017
Full Text
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7. Using CD4 percentage and age to optimize pediatric antiretroviral therapy initiation

Author

Yin, D.E., Warshaw, M.G., Miller, W.C., Castro, H., Fiscus, S.A., Harper, L.M., Harrison, L.J., Klein, N.J., Lewis, J., Melvin, A.J., Tudor Williams, G., Mckinney, R.E., Brouwers, P., Costello, D., Ferguson, E., Fiscus, S., Hodge, J., Hughes, M., Jennings, C., Melvin, A., Mckinney, R., Mofenson, L., Warshaw, M., Smith, M., Spector, S., Stiehm, E., Toye, M., Yogev, R., Babiker, A., Compagnucci, A., De Rossi, A., Giaquinto, C., Darbyshire, J., Debré, M., Gibb, D., Harper, L., Harrison, L., Klein, N., Pillay, D., Saidi, Y., Walker, A., Brody, B., Hill, C., Lepage, P., Modlin, J., Poziak, A., Rein, M., Robb, M., Fleming, T., Vella, S., Kim, K., Bologna, R., Mecikovsky, D., Pineda, N., Sen, L., Mangano, A., Marino, S., Galvez, C., Deluchi, G., Zöhrer, B., Zenz, W., Daghofer, E., Pfurtscheller, K., Pabst, B., Gomez, M., Mcneil, P., Jervis, M., Whyms, I., Kwolfe, D., Scott, S., Mussi Pinhata MM, Issac, M., Cervi, M., Negrini, B., Matsubara, T., de Souza CB, Gabaldi, J., Oliveira, R., Sapia, M., Abreu, T., Evangelista, L., Pala, A., Fernandes, I., Farias, I., Melo M, D.F., Carreira, H., Lira, L., Della Negra, M., Queiroz, W., Lian, Y., Pacola, D., Pinto, J., Ferreira, F., Kakehasi, F., Martins, L., Diniz, A., Lobato, V., Diniz, M., Cleto, S., Costa, S., Romeiro, J., Dollfus, C., Tabone, M., Courcoux, M., Vaudre, G., Dehée, A., Schnuriger, A., Le Gueyades, N., De Bortoli, C., Méchinaud, F., Reliquet, V., Arias, J., Rodallec, A., André, E., Falconi, I., Le Pelletier, A., Monpoux, F., Cottalorda, J., Mellul, S., Lachassinne, E., Galimand, J., Rouzioux, C., Chaix, M., Benabadji, Z., Pourrat, M., Firtion, G., Rivaux, D., Denon, M., Boudjoudi, N., Nganzali, F., Krivine, A., Méritet, J., Delommois, G., Norgeux, C., Guérin, C., Floch, C., Marty, L., Hichou, H., Tournier, V., Faye, A., Le Moal, I., Sellier, M., Dehache, L., Damond, F., Leleu, J., Beniken, D., Alexandre Castor, G., Neubert, J., Niehues, T., Laws, H., Huck, K., Gudowius, S., Siepermann, K., Loeffler, H., Bellert, S., Ortwin, A., Notheis, G., Wintergerst, U., Hoffman, F., Werthmann, A., Seyboldt, S., Schneider, L., Bucholz, B., Feiterna Sperling, C., Peiser, C., Nickel, R., Schmitz, T., Piening, T., Müller, C., Warncke, G., Wigger, M., Neubauer, R., Butler, K., Chong, A., Boulger, T., Menon, A., O'Connell, M., Barrett, L., Rochford, A., Goode, M., Hayes, E., Mcdonagh, S., Walsh, A., Doyle, A., Fanning, J., O'Connor, M., Byrne, M., O'Sullivan, N., Hyland, E., Giacomet, V., Viganò, A., Colombo, I., Trabattoni, D., Berzi, A., Badolato, R., Schumacher, F., Bennato, V., Brusati, M., Sorlini, A., Spinelli, E., Filisetti, M., Bertulli, C., Rampon, O., Zanchetta, M., Mazza, A., Stringari, G., Rossetti, G., Bernardi, S., Martino, A., Castelli Gattinara, G., Palma, P., Pontrelli, G., Tchidjou, H., Furcas, A., Frillici, C., Mazzei, A., Zoccano, A., Concato, C., Duiculescu, D., Oprea, C., Tardei, G., Abaab, F., Mardarescu, M., Draghicenoiu, R., Otelea, D., Alecsandru, L., Matusa, R., Rugina, S., Ilie, M., Netescu, S., Florea, C., Voicu, E., Poalelungi, D., Belmega, C., Vladau, L., Chiriac, A., Ramos Amador JT, Gonzalez Tomé MI, Rojo Conejo, P., Fernandez, M., Delgado Garcia, R., Ferrari, J., Garcia Lopez, M., Mellado Peña MJ, Martin Fontelos, P., Jimenez Nacher, I., Muñoz Fernandez MA, Jimenez, J., García Torre, A., Penin, M., Pineiro Perez, R., Garcia Mellado, I., Finn, A., Lajeunesse, M., Hutchison, E., Usher, J., Ball, L., Dunn, M., Sharland, M., Doerholt, K., Storey, S., Donaghy, S., Chakraborty, R., Wells, C., Buckberry, K., Rice, P., Mcmaster, P., Butler, P., O'Connell C, R., Shenton, J., Haley, H., Orendi, J., Stroobant, J., Navarante, L., Archer, P., Mazhude, C., Scott, D., O'Connell, R., Wong, J., Boddy, G., Shackley, F., Lakshman, R., Hobbs, J., Ball, G., Kudesia, G., Bane, J., Painter, D., Sloper, K., Shah, V., Cheng, A., Aali, A., Ball, C., Hawkins, S., Nayagam, D., Waters, A., Doshi, S., Liebeschuetz, S., Sodiende, B., Shingadia, D., Wong, S., Swan, J., Shah, Z., Collinson, A., Hayes, C., King, J., O'Connor, K., Lyall, H., Fidler, K., Walters, S., Foster, C., Hamadache, D., Newbould, C., Monrose, C., Campbell, S., Yeung, S., Cohen, J., Martinez Allier, N., Melvin, D., Dodge, J., Welch, S., Tatum, G., Gordon, A., Kaye, S., Muir, D., Patel, D., Novelli, V., Moshal, K., Lambert, J., Flynn, J., Farrelly, L., Clapson, M., Spencer, L., Depala, M., Jacobsen, M., Segal, S., Pollard, A., Kelly, D., Yeadon, S., Ohene Kena, B., Peng, Y., Dong, T., Jeffries, K., Snelling, M., Smyth, A., Smith, J., Ward, B., Jungmann, E., Ryan, C., Swaby, K., Buckton, A., Smit, E., Abrams, E., Champion, S., Fernandez, A., Calo, D., Garrovillo, L., Swaminathan, K., Alford, T., Frere, M., Navarra, J., Borkowsky, W., Deygoo, S., Hastings, T., Akleh, S., Ilmet, T., Mohan, K., Bowen, G., Emmanuel, P., Lujan Zimmerman, J., Rodriguez, C., Johnson, S., Marion, A., Graisbery, C., Casey, D., Lewis, G., Guzman Cottrill, J., Croteau, R., Acevedo Flores, M., Gonzalez, M., Angeli, L., Fabregas, L., Valentin, P., Weiner, L., Contello, K., Holz, W., Butler, M., Nachman, S., Kelly, M., Ferraro, D., Rana, S., Reed, C., Yeagley, E., Malheiro, A., Roa, J., Neely, M., Kovacs, A., Homans, J., Rodriguez Lozano, Y., Puga, A., Talero, G., Sellers, R., Lawrence, R., Weinberg, G., Murante, B., Laverty, S., Deveikis, A., Batra, J., Chen, T., Michalik, D., Deville, J., Elkins, K., Marks, S., Jackson Alvarez, J., Palm, J., Fineanganofo, I., Keuth, M., Deveikis, L., Tomosada, W., Van Dyke, R., Alchediak, T., Silio, M., Borne, C., Bradford, S., Eloby Childress, S., Nguyen, K., Rathore, M., Alvarez, A., Mirza, A., Mahmoudi, S., Burke, M., Febo, I., Lugo, L., Santos, R., Church, J., Dunaway, T., Rodier, C., Flynn, P., Patel, N., Discenza, S., Donohoe, M., Luzuriaga, K., Picard, D., Kline, M., Paul, M., Shearer, W., Mcmullen, C., Chadwick, E., Cagwin, E., Kabat, K., Dieudonne, A., Palumbo, P., Johnson, J., Gaur, S., Cerracchio, L., Foca, M., Jurgrau, A., Vasquez Bonilla, S., Silva, G., Gershon, A., Sullivan, J., Bryson, Y., Frenkel, L., Nelson, J., Aboulker, J., Hadjou, G., Léonardo, S., Riault, Y., Saïdi, Y., Buck, L., Forcat, S., Horton, J., Johnson, D., Moore, S., Taylor, C., Collins, D., Buskirk, S., Kamara, P., Nesel, C., Johnson, M., Ferreira, A., Tutko, J., Sprenger, H., Britto, P., Powell, C., Dersimonian, R., Handelsman, E., Ananworanich, J., Belfrage, E., Blanche, S., Bohlin, A., Burger, D., Clayden, P., De Groot, R., Di Biagio, A., Grosch Wörner, I., Hainault, M., Lallemant, M., Levy, J., Marczynska, M., Mellado Pena MJ, Nadal, D., Naver, L., Peckham, C., Popieska, J., Rosado, L., Rosso, R., Rudin, C., Scherpbier, H., Stevanovic, M., Thorne, C., Tovo, P., Valerius, N., Poole, C., Cole, S., and Mcculloh, R.J.

Subjects
CD4-Positive T-Lymphocytes, Male, medicine.medical_treatment, HIV (FISIOLOGIA), lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, Treatment failure, Settore BIO/13 - Biologia Applicata, Antiretroviral Therapy, Highly Active, immunologic, Child, HIV, child, reconstitution, treatment failure, Adolescent, Anti-HIV Agents, CD4 Lymphocyte Count, Child, Preschool, Female, Follow-Up Studies, HIV-1, Humans, Infant, Infant, Newborn, Follow up studies, Immunosuppression, medicine.medical_specialty, Settore MED/17 - Malattie Infettive, Antiretroviral Therapy, World health, Article, Internal medicine, medicine, Highly Active, Preschool, Settore MED/04 - Patologia Generale, business.industry, Disease progression, Settore MED/46 - Scienze Tecniche di Medicina di Laboratorio, Newborn, Antiretroviral therapy, Confidence interval, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Immunologic, Reconstitution, Pediatrics, Perinatology and Child Health, Immunology, business
Abstract

BACKGROUND: Quantifying pediatric immunologic recovery by highly active antiretroviral therapy (HAART) initiation at different CD4 percentage (CD4%) and age thresholds may inform decisions about timing of treatment initiation. METHODS: HIV-1-infected, HAART-naive children in Europe and the Americas were followed from 2002 through 2009 in PENPACT-1. Data from 162 vertically infected children, with at least World Health Organization “mild” immunosuppression and CD4% RESULTS: Seventy-two percent of baseline immunosuppressed children recovered to normal within 4 years. Compared with “severe” immunosuppression, more children with “mild” immunosuppression (difference 36%, 95% confidence interval [CI]: 22% to 49%) or “advanced” immunosuppression (difference 20.8%, 95% CI: 5.8% to 35.9%) recovered a normal CD4%. For each 5-year increase in baseline age, the proportion of children achieving a normal CD4% declined by 19% (95% CI: 11% to 27%). Combining baseline CD4% and age effects resulted in >90% recovery when initiating HAART with “mild” immunosuppression at any age or “advanced” immunosuppression at age CONCLUSIONS: Initiating HAART at higher CD4% and younger ages maximizes potential for immunologic recovery. Guidelines should weigh immunologic benefits against long-term risks.

Published
2014

8. The immunological and virological consequences of planned treatment interruptions in children with HIV infection

Author

Klein, Nigel, Sefe, Delali, Mosconi, Ilaria, Zanchetta, Marisa, Castro, Hannah, Jacobsen, Marianne, Jones, Hannah, Bernardi, Stefania, Pillay, Deenan, Giaquinto, Carlo, Walker, A. Sarah, Gibb, Diana M., De Rossi, Anita, Paediatric, European Network for Treatment of AIDS 11 Trial Team including Aboulker JP, Ananworanich, J, Babiker, A, Belfrage, E, Bernardi, S, Blanche, S, Bohlin, Ab, Bologna, R, Burger, Dm, Butler, K, Castelli Gattinara, G, Castro, H, Clayden, P, Compagnucci, A, Darbyshire, Jh, Debré, M, Faye, A, de Groot, R, della Negra, M, Duiculescu, D, Giaquinto, C, Gibb, Dm, Grosch Wörner, I, Hainault, M, Harper, L, Klein, N, Lallemant, M, Levy, J, Lyall, H, Marczynska, M, Mardarescu, M, Mellado Peña, Mj, Nadal, D, Niehues, T, Peckham, C, Pillay, D, Ramos Amador, Jt, Rosado, L, Rosso, R, Rudin, C, Saidi, Y, Scherpbier, Hj, Sharland, M, Stevanovic, M, Thorne, C, Tovo, Pier Angelo, Tudor Williams, G, Valerius, N, Walker, As, Welch, S, Wintergerst, U, Aboulker, Jp, Mofenson, L, Moye, J, Saïdi, Y, Cressey, Tr, Jacqz Aigrain, E, Khoo, S, Tréluyer, Jm, De Rossi, A, Ngo Giang Huong, N, Muñoz Fernandez, Ma, Hill, C, Lepage, P, Pozniak, A, Vella, S, Hadjou, G, Léonardo, S, Riault, Y, Buck, L, Farrelly, L, Forcat, S, Harrison, L, Horton, J, Johnson, D, Moore, S, Taylor, C, Chalermpantmetagul, S, Peongjakta, R, Chailert, S, Fregonese, F, Jourdain, G, Butler, D, Carlton, C, Collins, D, Kao, G, Van Buskirk, S, Watson, S, Corradini, S, Floret, D, Le Thi, Tt, Monpoux, F, Cottalorda, J, Lefebvre, Jc, Mellul, S, Boudjoudi, N, Firtion, G, Denon, M, Picard, F, Beniken, D, Damond, F, Alexandre, G, Tricoire, J, Nicot, F, Krivine, A, Rivaux, D, Chaix, Ml, Notheis, G, Strotmann, G, Schlieben, S, Rampon, O, Zanchetta, M, Ginocchio, F, Viscoli, C, Martino, A, Pontrelli, G, Concato, C, Mazza, A, Rossetti, G, Dobosz, S, Oldakowska, A, Popielska, J, Kaflik, M, Stanczak, J, Stanczack, G, Dyda, T, González Tomé, Mi, Delgado García, R, Fernandez Gonzalez, Mt, Martín Fontelos, P, Piñeiro Pérez, R, Penin, M, Garcia Mellado, I, Medina, Af, Ascencion, B, Garcia Bermejo, I, Garcia Vela, Ja, Martin Rubio, I, Gurbindo, D, Navarro Gomez, Ml, Jimenez, Jl, Garcia Torre, A, José Gómez, Mi, García Rodriguez, Mc, Moreno Pérez, D, Núñez Cuadros, E, Asensi Botet, F, Pérez, A, Pérez Tamarit, Md, Gobernado Serrano, M, Gonzales Molina, A, Kalhert, C, Dobrovoljac, M, Berger, C, Nobile, G, Reinhard, S, Schupbach, J, Bunupuradah, T, Puthanakit, T, Pancharoen, C, Butterworth, O, Phasomsap, C, Jupimai, T, Ubolyam, S, Phanuphak, P, Mai, C, Kanjanavanit, S, Namwong, T, Chutima, D, Raksasang, M, Foster, C, Hamadache, D, Campbell, S, Newbould, C, Monrose, C, Patel, D, Kaye, S, Seery, P, Wildfire, A, Novelli, V, Shingadia, D, Moshal, K, Flynn, J, Clapson, M, Allen, A, Spencer, L, Depala, M, Jacobsen, M, Mcmaster, P, Phipps, M, Orendi, J, Farmer, C, Liebeschuetz, S, Sodeinde, O, Wong, S, Heath, Y, Scott, S, Gandhi, K, Lewis, P, Daglish, J, Weiner, L, Famiglietti, M, Rana, S, Yu, P, Roa, J, Puga, A, Haerry, A, and Inma, A.

Subjects
CD31, Genetics and Molecular Biology (all), CD4-Positive T-Lymphocytes, Time Factors, T-CELL RECONSTITUTION, ACTIVE ANTIRETROVIRAL THERAPY, STRUCTURED TREATMENT INTERRUPTION, T-CELL RECONSTITUTION, HIV-1-INFECTED CHILDREN, IMMUNE RECONSTITUTION, THYMIC OUTPUT, 1-INFECTED CHILDREN, Adolescent, Anti-Retroviral Agents, CD8-Positive T-Lymphocytes, Child, Child, Preschool, Drug Administration Schedule, HIV Infections, Humans, Immunophenotyping, Lymphocyte Count, Treatment Outcome, Viral Load, Agricultural and Biological Sciences (all), Biochemistry, Genetics and Molecular Biology (all), Medicine (all), Biochemistry, law.invention, IMMUNE RECONSTITUTION, 0302 clinical medicine, Randomized controlled trial, law, 030212 general & internal medicine, HIV-1-INFECTED CHILDREN, 0303 health sciences, Multidisciplinary, ACTIVE ANTIRETROVIRAL THERAPY, 3. Good health, Medicine, Off Treatment, Poverty-related infectious diseases Infectious diseases and international health [N4i 3], THYMIC OUTPUT, Viral load, Research Article, Science, 1-INFECTED CHILDREN, Auto-immunity, transplantation and immunotherapy [N4i 4], 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), medicine, Preschool, 030304 developmental biology, business.industry, medicine.disease, Clinical trial, Immunology, STRUCTURED TREATMENT INTERRUPTION, business, CD8
Abstract

Contains fulltext : 126098.pdf (Publisher’s version ) (Open Access) OBJECTIVES: To evaluate the immunological and viral consequences of planned treatment interruptions (PTI) in children with HIV. DESIGN: This was an immunological and virological sub-study of the Paediatric European Network for Treatment of AIDS (PENTA) 11 trial, which compared CD4-guided PTI of antiretroviral therapy (ART) with continuous therapy (CT) in children. METHODS: HIV-1 RNA and lymphocyte subsets, including CD4 and CD8 cells, were quantified on fresh samples collected during the study; CD45RA, CD45RO and CD31 subpopulations were evaluated in some centres. For 36 (18 PTI, 18 CT) children, immunophenotyping was performed and cell-associated HIV-1 DNA analysed on stored samples to 48 weeks. RESULTS: In the PTI group, CD4 cell count fell rapidly in the first 12 weeks off ART, with decreases in both naive and memory cells. However, the proportion of CD4 cells expressing CD45RA and CD45RO remained constant in both groups. The increase in CD8 cells in the first 12 weeks off ART in the PTI group was predominantly due to increases in RO-expressing cells. PTI was associated with a rapid and sustained increase in CD4 cells expressing Ki67 and HLA-DR, and increased levels of HIV-1 DNA. CONCLUSIONS: PTI in children is associated with rapid changes in CD4 and CD8 cells, likely due to increased cell turnover and immune activation. However, children off treatment may be able to maintain stable levels of naive CD4 cells, at least in proportion to the memory cell pool, which may in part explain the observed excellent CD4 cell recovery with re-introduction of ART.

Published
2013

9. Verticale HIV-I-transmissie. I. Risico en preventie bij de zwangere

Author

Orendi, J. M., Boer, K., van Loon, A. M., Borleffs, J. C., van Oppen, A. C., Boucher, C. A., and Other departments

Subjects
virus diseases
Abstract

Without anti-HIV treatment, mother to child HIV-I transmission occurs in 15-30% of HIV positive pregnancies. Transmission occurs mostly in the last trimester or at birth. The maternal virus load in the last trimester and around birth is strongly related to the risk of HIV transmission to the child. This risk can be reduced during pregnancy by anti-HIV treatment and in certain cases by performing a caesarean section. It is recommended to determine the plasma virus load several times during pregnancy. If the virus load is found to be high, measurement of plasma anti-HIV drug concentrations and anti-HIV drug resistance may prompt modification of the anti-HIV drug regimen with the objective of achieving maximal suppression of virus replication in the last trimester

Published
1998

10. Whole-Genome Sequencing Reveals the Contribution of Long-Term Carriers in Staphylococcus aureusOutbreak Investigation

Author

Gordon, N. C., Pichon, B., Golubchik, T., Wilson, D. J., Paul, J., Blanc, D. S., Cole, K., Collins, J., Cortes, N., Cubbon, M., Gould, F. K., Jenks, P. J., Llewelyn, M., Nash, J. Q., Orendi, J. M., Paranthaman, K., Price, J. R., Senn, L., Thomas, H. L., Wyllie, S., Crook, D. W., Peto, T. E. A., Walker, A. S., and Kearns, A. M.

Abstract

ABSTRACTWhole-genome sequencing (WGS) makes it possible to determine the relatedness of bacterial isolates at a high resolution, thereby helping to characterize outbreaks. However, for Staphylococcus aureus, the accumulation of within-host diversity during carriage might limit the interpretation of sequencing data. In this study, we hypothesized the converse, namely, that within-host diversity can in fact be exploited to reveal the involvement of long-term carriers (LTCs) in outbreaks. We analyzed WGS data from 20 historical outbreaks and applied phylogenetic methods to assess genetic relatedness and to estimate the time to most recent common ancestor (TMRCA). The findings were compared with the routine investigation results and epidemiological evidence. Outbreaks with epidemiological evidence for an LTC source had a mean estimated TMRCA (adjusted for outbreak duration) of 243 days (95% highest posterior density interval [HPD], 143 to 343 days) compared with 55 days (95% HPD, 28 to 81 days) for outbreaks lacking epidemiological evidence for an LTC (P= 0.004). A threshold of 156 days predicted LTC involvement with a sensitivity of 0.875 and a specificity of 1. We also found 6/20 outbreaks included isolates with differing antimicrobial susceptibility profiles; however, these had only modestly increased pairwise diversity (mean 17.5 single nucleotide variants [SNVs] [95% confidence interval {CI}, 17.3 to 17.8]) compared with isolates with identical antibiograms (12.7 SNVs [95% CI, 12.5 to 12.8]) (P< 0.0001). Additionally, for 2 outbreaks, WGS identified 1 or more isolates that were genetically distinct despite having the outbreak pulsed-field gel electrophoresis (PFGE) pulsotype. The duration-adjusted TMRCA allowed the involvement of LTCs in outbreaks to be identified and could be used to decide whether screening for long-term carriage (e.g., in health care workers) is warranted. Requiring identical antibiograms to trigger investigation could miss important contributors to outbreaks.

Published
2017
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14. Community and nosocomial transmission of Panton-Valentine leucocidin-positive community-associated meticillin-resistant Staphylococcus aureus: implications for healthcare.

Author

Orendi JM, Coetzee N, Ellington MJ, Boakes E, Cookson BD, Hardy KJ, Hawkey PM, Kearns AM, Orendi, J M, Coetzee, N, Ellington, M J, Boakes, E, Cookson, B D, Hardy, K J, Hawkey, P M, and Kearns, A M

Abstract

In the UK, infections due to Panton-Valentine leucocidin-positive community-associated meticillin-resistant Staphylococcus aureus (PVL-MRSA) have been reported sporadically. In September 2006, a fatal PVL-MRSA infection occurred in a Filipino healthcare worker (HCW) after she underwent caesarean section. Throat and nasal swabs were obtained from contacts of cases in community and hospital. MRSA with an antibiogram similar to the PVL-MRSA strain were characterised including toxin gene profiling, polymerase chain reaction- and sequence-based typing. Carriers underwent decolonisation treatment, and HCWs were restricted from patient care until they and their household members were considered negative for PVL-MRSA. The PVL-MRSA belonged to ST30, was protein A gene (spa) type t019, SCCmec IVc, agr 3, and resistant only to beta-lactam antibiotics. Representatives of the same lineage were identified among a further 16 individuals in community and hospital. Infections likely to be caused by PVL-MRSA had occurred in 12 cases, and were likely to be hospital-acquired in two patients (one fatal) and occupationally acquired in one HCW. Nine cases worked as nursing staff in the hospital. Eight of these had emigrated from the Philippines in the previous five years and were linked socially. Thus, PVL-MRSA-ST30 was detected in a HCW community in the UK. This is the first report of nosocomial transmission of this pandemic clone in the UK associated with a fatality. Increased vigilance in healthcare and community is needed in response to this emerging threat. [ABSTRACT FROM AUTHOR]

Published
2010
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15. Single-dose cefuroxime with gentamicin reduces Clostridium difficile-associated disease in hip-fracture patients.

Author

Starks, I., Ayub, G., Walley, G., Orendi, J., Roberts, P., and Maffulli, N.

Abstract

Summary: Antibiotic-associated Clostridium difficile diarrhoea may complicate recovery from surgery for proximal femoral fracture. We undertook a four-year case–control study to evaluate a change in antibiotic prophylaxis in our department. During the period January 2003 to January 2005, patients received three doses of prophylactic cefuroxime (1.5g). We then introduced a new regimen, comprising of one single dose of cefuroxime (1.5g) with gentamicin (240mg) at induction. Prior to the change in prophylaxis, 912 patients underwent surgery for neck of femur fracture, and from March 2005 to March 2007, 899 patients had surgery under the new regimen. Thirty-eight patients developed C. difficile infection (4.2%) in the initial group, compared with 14 patients (1.6%) in the group with the new regimen (P =0.009). The incidence of C. difficile infection increased throughout the rest of the hospital over the same time period. Patients with C. difficile infection had a statistically significant increase in antibiotic exposure, inpatient stay, morbidity and inpatient mortality. The main challenges regarding prophylactic antibiotic selection are infection due to meticillin-resistant Staphylococcus aureus (MRSA) and C. difficile-associated diarrhoea. We advocate the use of the new regimen as an alternative to multiple-dose cephalosporin antibiotics for the prevention of C. difficile infection in this group of high-risk patients. [Copyright &y& Elsevier]

Published
2008
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18. A two-stage algorithm for Clostridium difficile including PCR: can we replace the toxin EIA?

Author

Orendi JM, Monnery DJ, Manzoor S, and Hawkey PM

Subjects
Aged, Aged, 80 and over, Algorithms, Antigens, Bacterial analysis, Child, Child, Preschool, Clostridioides difficile isolation & purification, Clostridium Infections microbiology, Feces chemistry, Feces microbiology, Humans, Immunoenzyme Techniques methods, Bacterial Toxins analysis, Bacterial Toxins genetics, Clinical Laboratory Techniques methods, Clostridioides difficile genetics, Clostridium Infections diagnosis, Polymerase Chain Reaction methods
Abstract

A two step, three-test algorithm for Clostridium difficile infection (CDI) was reviewed. Stool samples were tested by enzyme immunoassays for C. difficile common antigen glutamate dehydrogenase (G) and toxin A/B (T). Samples with discordant results were tested by polymerase chain reaction detecting the toxin B gene (P). The algorithm quickly identified patients with detectable toxin A/B, whereas a large group of patients excreting toxigenic C. difficile but with toxin A/B production below detection level (G(+)T(-)P(+)) was identified separately. The average white blood cell count in patients with a G(+)T(+) result was higher than in those with a G(+)T(-)P(+) result., (Copyright © 2011 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Published
2012
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19. Methicillin resistant Staphylococcus aureus (MRSA) is not always caught on the orthopaedic ward.

Author

Walley G, Orendi J, Bridgman S, Davis B, Ahmed el-N, and Maffulli N

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Cross Infection prevention & control, England epidemiology, Female, Hospitals, University, Humans, Male, Middle Aged, Orthopedic Procedures, Prevalence, Staphylococcal Infections prevention & control, Surgical Wound Infection epidemiology, Cross Infection epidemiology, Methicillin-Resistant Staphylococcus aureus, Staphylococcal Infections epidemiology, Wound Infection epidemiology
Abstract

We report the prevalence and incidence of methicillin-resistant Staphylococcus aureus (MRSA) colonisation during the patient journey for patients admitted to orthopaedic and trauma wards. Patients were swabbed for MRSA colonisation on admission, transfer, and discharge from hospital. Elective patients undergoing major joint surgery were also swabbed at a pre-operative assessment clinic. Of the 559 patients admitted, 323 (101 elective, 192 trauma and 30 non-orthopaedic) were included in the study. Of these, 27 elective (27%), 41 trauma (21%), and seven non-orthopaedic (23%) patients were colonised with MRSA at any time during the audit period. There is a high prevalence of MRSA colonisation in patients admitted to the orthopaedic and trauma wards in our setting. A policy of pre-admission screening, though able to identify MRSA carriage, does not guarantee that patients are not colonised in the period between screening and admission. We suggest to screen for MRSA all patients admitted to an orthopaedic ward.

Published
2009

20. MRSA screening: operational strategies.

Author

Orendi JM

Subjects
Humans, Prevalence, State Medicine statistics & numerical data, United Kingdom epidemiology, Cross Infection economics, Cross Infection epidemiology, Cross Infection prevention & control, Infection Control economics, Infection Control methods, Infection Control standards, Methicillin-Resistant Staphylococcus aureus isolation & purification, Staphylococcal Infections economics, Staphylococcal Infections epidemiology, Staphylococcal Infections prevention & control
Published
2009
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21. Atypical presentation of Streptococcus zooepidemicus bacteraemia and secondary meningitis.

Author

Pati S, Al-Araji A, and Orendi J

Subjects
Adult, Agricultural Workers' Diseases drug therapy, Agricultural Workers' Diseases microbiology, Bacteremia drug therapy, Bacteremia microbiology, Ceftriaxone therapeutic use, Diagnosis, Differential, Humans, Magnetic Resonance Imaging, Male, Meningitis, Bacterial drug therapy, Meningitis, Bacterial microbiology, Microbial Sensitivity Tests, Sinusitis drug therapy, Sinusitis microbiology, Streptococcal Infections drug therapy, Streptococcal Infections microbiology, Tomography, X-Ray Computed, Virulence, Agricultural Workers' Diseases diagnosis, Bacteremia diagnosis, Meningitis, Bacterial diagnosis, Sinusitis diagnosis, Streptococcal Infections diagnosis, Streptococcus equi pathogenicity
Published
2007
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22. Mother-to-child transmission of Burkholderia pseudomallei.

Author

Abbink FC, Orendi JM, and de Beaufort AJ

Subjects
Adult, Cervix Uteri microbiology, Female, Humans, Placenta Previa, Pregnancy, Sepsis microbiology, Burkholderia pseudomallei isolation & purification, Infectious Disease Transmission, Vertical, Melioidosis transmission
Published
2001
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23. [Vertical HIV-I-transmission. I. Risk and prevention in pregnancy].

Author

Orendi JM, Boer K, van Loon AM, Borleffs JC, van Oppen AC, and Boucher CA

Subjects
Adolescent, Adult, Antiviral Agents therapeutic use, CD4 Lymphocyte Count, Drug Therapy, Combination, Female, HIV Infections diagnosis, HIV Infections prevention & control, HIV-1 isolation & purification, Humans, Infant, Newborn, Maternal-Fetal Exchange, Pregnancy, Pregnancy Complications, Infectious diagnosis, Pregnancy Trimester, Third, Risk Assessment, Viral Load, HIV Infections transmission, HIV-1 pathogenicity, Infectious Disease Transmission, Vertical prevention & control, Pregnancy Complications, Infectious prevention & control, Prenatal Exposure Delayed Effects
Abstract

Without anti-HIV treatment, mother to child HIV-I transmission occurs in 15-30% of HIV positive pregnancies. Transmission occurs mostly in the last trimester or at birth. The maternal virus load in the last trimester and around birth is strongly related to the risk of HIV transmission to the child. This risk can be reduced during pregnancy by anti-HIV treatment and in certain cases by performing a caesarean section. It is recommended to determine the plasma virus load several times during pregnancy. If the virus load is found to be high, measurement of plasma anti-HIV drug concentrations and anti-HIV drug resistance may prompt modification of the anti-HIV drug regimen with the objective of achieving maximal suppression of virus replication in the last trimester.

Published
1998

24. [Vertical HIV-I-transmission. II. HIV-diagnosis in a child].

Author

Orendi JM, Geelen SP, de Graeff-Meeder ER, van Loon AM, Schuurman R, and Boucher CA

Subjects
Adult, CD4 Lymphocyte Count methods, Female, HIV Infections transmission, HIV-1 isolation & purification, Humans, Infant, Infant, Newborn, Infectious Disease Transmission, Vertical prevention & control, Male, Polymerase Chain Reaction, Pregnancy, Pregnancy Complications, Infectious, AIDS-Related Opportunistic Infections prevention & control, Anti-HIV Agents therapeutic use, Antibiotic Prophylaxis, HIV Infections diagnosis, HIV-1 pathogenicity, Infant, Newborn, Diseases diagnosis
Abstract

In newborn children from HIV-infected women early establishment of HIV infection is of importance for optimal therapy of HIV-infected children and avoidance of unnecessary medication in uninfected children. A more than 95% reliable diagnosis of HIV infection can now be obtained at the age of four weeks by polymerase chain reaction (PCR) technology. Before this age a positive PCR result is relevant since it necessitates additional investigation such as measuring anti-HIV drug resistance and may lead to modification of anti-HIV treatment. Prophylaxis against Pneumocystis carinii is not needed if HIV infection can not be demonstrated by PCR after the age of four weeks.

Published
1998

25. Activation and cell cycle antigens in CD4+ and CD8+ T cells correlate with plasma human immunodeficiency virus (HIV-1) RNA level in HIV-1 infection.

Author

Orendi JM, Bloem AC, Borleffs JC, Wijnholds FJ, de Vos NM, Nottet HS, Visser MR, Snippe H, Verhoef J, and Boucher CA

Subjects
ADP-ribosyl Cyclase, ADP-ribosyl Cyclase 1, Adult, Antigens, Differentiation analysis, Biomarkers, HIV Infections virology, Humans, Ki-67 Antigen analysis, Lymphocyte Activation, Membrane Glycoproteins, Middle Aged, NAD+ Nucleosidase analysis, beta 2-Microglobulin analysis, Antigens, CD, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, HIV Antigens analysis, HIV Infections immunology, HIV-1 growth & development, RNA, Viral blood, Virus Replication immunology
Abstract

The relationship between T cell activation and human immunodeficiency virus type 1 (HIV-1) replication was studied in HIV-infected subjects, 20 with and 10 without anti-HIV treatment. Expression of Ki-67 proliferation-associated antigen was increased in CD4+ and CD8+ T cells and correlated with HLA-DR. In subjects without anti-HIV treatment, the plasma HIV-1 RNA level correlated with HLA-DR in CD4+ T cells, with Ki-67 in CD8+ T cells, and with expression of CD38 in both T cell subsets. A proportion of treated subjects had increased T cell activation despite 4 months of highly active antiretroviral treatment (HAART). In subjects receiving HAART, a high percentage of HLA-DR+ CD4+ T cells was associated with signs of opportunistic infections. This work supports the concept that, in the natural course of HIV-1 infection, HIV replication itself leads to general T cell activation and that opportunistic infections generate additional CD4+ T cell activation and HIV replication.

Published
1998
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26. A Developmental Functional MRI Study of Prefrontal Activation during Performance of a Go-No-Go Task.

Author

Casey BJ, Trainor RJ, Orendi JL, Schubert AB, Nystrom LE, Giedd JN, Castellanos FX, Haxby JV, Noll DC, Cohen JD, Forman SD, Dahl RE, and Rapoport JL

Abstract

This study examines important developmental differences in patterns of activation in the prefrontal cortex during performance of a Go-No-Go paradigm using functional magnetic resonance imaging (fMRI). Eighteen subjects (9 children and 9 adults) were scanned using gradient echo, echo planar imaging during performance of a response inhibition task. The results suggest four general findings. First, the location of activation in the prefrontal cortex was not different between children and adults, which is similar to our earlier pediatric fMRI results of prefrontal activation during a working memory task (Casey et al., 1995). Second, the volume of activation was significantly greater for children relative to adults. These differences in volume of activation were observed predominantly in the dorsal and lateral prefrontal cortices. Third, although inhibitory processes have typically been associated with more ventral or orbital frontal regions, the current study revealed activation that was distributed across both dorsolateral and orbitofrontal cortices. Finally, consistent with animal and human lesion studies, activity in orbital frontal and anterior cingulate cortices correlated with behavioral performance (i.e., number of false alarms). These results further demonstrate the utility of this methodology in studying pediatric populations.

Published
1997
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27. Functional magnetic resonance imaging studies of emotional processing in normal and depressed patients: effects of venlafaxine.

Author

Kalin NH, Davidson RJ, Irwin W, Warner G, Orendi JL, Sutton SK, Mock BJ, Sorenson JA, Lowe M, and Turski PA

Subjects
Adolescent, Adult, Brain anatomy & histology, Brain drug effects, Cyclohexanols therapeutic use, Depressive Disorder drug therapy, Depressive Disorder psychology, Echo-Planar Imaging, Emotions drug effects, Female, Humans, Male, Middle Aged, Psychiatric Status Rating Scales, Selective Serotonin Reuptake Inhibitors therapeutic use, Treatment Outcome, Venlafaxine Hydrochloride, Visual Cortex anatomy & histology, Visual Cortex drug effects, Visual Cortex physiology, Visual Perception physiology, Brain physiology, Cyclohexanols pharmacology, Depressive Disorder diagnosis, Emotions physiology, Magnetic Resonance Imaging, Selective Serotonin Reuptake Inhibitors pharmacology
Abstract

Background: Functional magnetic resonance imaging (fMRI) techniques were used to identify the neural circuitry underlying emotional processing in control and depressed subjects. Depressed subjects were studied before and after treatment with venlafaxine. This new technique provides a method to noninvasively image regional brain function with unprecedented spatial and temporal resolution., Method: Echo-planar imaging was used to acquire whole brain images while subjects viewed positively and negatively valenced visual stimuli. Two control subjects and two depressed subjects who met DSM-IV criteria for major depression were scanned at baseline and 2 weeks later. Depressed subjects were treated with venlafaxine after the baseline scan., Results: Preliminary results from this ongoing study revealed three interesting trends in the data. Both depressed patients demonstrated considerable symptomatic improvement at the time of the second scan. Across control and depressed subjects, the negative compared with the positive pictures elicited greater global activation. In both groups, activation induced by the negative pictures decreased from the baseline scan to the 2-week scan. This decrease in activation was also present in the control subjects when they were exposed to the positive pictures. In contrast, when the depressed subjects were presented with the positive pictures they showed no activation at baseline, whereas after 2 weeks of treatment an area of activation emerged in right secondary visual cortex., Conclusion: While preliminary, these results demonstrate the power of using fMRI to study emotional processes in normal and depressed subjects and to examine mechanisms of action of antidepressant drugs.

Published
1997

28. Enhancement of HIV-1 replication in peripheral blood mononuclear cells by Cryptococcus neoformans is monocyte-dependent but tumour necrosis factor-independent.

Author

Orendi JM, Nottet HS, Visser MR, Verheul AF, Snippe H, and Verhoef J

Subjects
Antibodies, Monoclonal immunology, Cells, Cultured, Humans, Monocytes cytology, Monocytes physiology, Pentoxifylline pharmacology, Tumor Necrosis Factor-alpha immunology, Virus Replication, Cryptococcus neoformans physiology, HIV-1 physiology, Monocytes microbiology, Tumor Necrosis Factor-alpha metabolism
Abstract

Objective: To investigate the possible role of Cryptococcus neoformans in HIV-1 pathogenesis., Design: An in vitro system was developed to study HIV-1 replication in freshly HIV-1-infected peripheral blood mononuclear cells (PBMC) incubated with whole azide-killed C. neoformans., Methods: Human PBMC or peripheral blood lymphocytes were infected with lymphocytotropic HIV-1 and incubated with azide-killed encapsulated or non-encapsulated C. neoformans for 10 days. Viral replication was followed by HIV-1 p24 enzyme-linked immunosorbent assay and median tissue culture infective dose determination. Tumour necrosis factor (TNF) release by PBMC, induced by C. neoformans, was measured. Anti-TNF monoclonal antibodies or pentoxifylline were used to inhibit TNF bioactivity., Results: Both encapsulated and non-encapsulated C. neoformans enhanced HIV-1 replication in PBMC but not in peripheral blood lymphocytes. C. neoformans induced TNF release by PBMC. Inhibition of TNF bioactivity did not block C. neoformans-enhanced HIV-1 replication in PBMC., Conclusions: C. neoformans can enhance HIV-1 replication in T cells only in the presence of monocytic cells. This enhancement is not dependent on encapsulation nor can it be attributed to TNF release.

Published
1994
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