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1. Management and outcome of patients with established coronary artery disease: the Euro Heart Survey on coronary revascularization

Author

Lenzen, M. J., Boersma, E., Bertrand, M. E., Maier, W., Moris, C., Piscione, F., Sechtem, U., Stahle, E., Widimsky, P., De Jaegere, P., Scholte Op Reimer, W. J. M., Mercado, N., Wijns, W., Meier, B., Sergeant, P., Vos, J., Unger, F., Manini, Malika, Bramley, Claire, Laforest, Valérie, Taylor, Charles, Del Gaiso, Susan, Huber, Kurt, De Backer, Guy, Sirakova, Vera, Cerbak, Roman, Thayssen, Per, Lehto, Seppo, Blanc, Jean-Jacques, Delahaye, François, Kobulia, Bondo, Zeymer, Uwe, Cokkinos, Dennis, Karlocai, Kristof, Graham, Ian, Shelley, Emer, Behar, Shlomo, Maggioni, Aldo, Grabauskiene, Virginija, Deckers, Jaap, Asmussen, Inger, Stepinska, Janina, Gonçalves, Lino, Mareev, Vyacheslav, Riecansky, Igor, Kenda, Miran F., Alonso, Angeles, Lopez-Sendon, José Luis, Rosengren, Annika, Buser, Peter, Okay, Tugrul, Sychov, Oleg, Fox, Kevin, Wood, David, Boersma, Eric, Crijns, Harry, Fox, Kim, McGregor, Keith, Mulder, Barbara, Priori, Sylvia, Rydén, Lars, Tavazzi, Luigi, Vahanian, Alec, Vardas, Panos, Wijns, William, Sarkisyan, Karine, Glogar, H. D., Derntl, Michael, Frick, Matthias, Pachinger, O., Zwick, Ralf, Vrints, Christiaan, Van Hertbruggen, Els, Vercammen, Marc, Sysmans, Tineke, Schroeder, E., Domange, Juliette, De Pril, Hilde, De Vriese, Johan, Van Hecke, Tonny, Legrand, V., Gillon, Marie-France, Richardy, Michel, Doneux, P., Petrov, Ivo, Jorgova, J., Starcevic, Boris, Eeckhout, Eric, Berger, Alexandre, Prudent, Veronique, Camenzind, E., Masson, Nicolas, Zambartas, Costas, Kleanthous, Helen, Widimsky, Petr, Stellova, Blanka, Aschermann, Michael, Simek, Stanislav, Kautzner, J., Karmazin, Vladimir, Svab, P., Indrak, Jan, Branny, M., Hladilova, Kveta, Kala, P., Thayssen, P., Cappelen, Helle, Jensen, Lisette Okkels, Gitt, A., Gehrke, Konstanze, Erbel, R., Gutersohn, Achim, Eggebrecht, Holger, Al Khani, Murad, Sechtem, Udo, Rosenberger, Antje, Vogelsberg, Holger, Klepzig, H., Schmidt, Arnold, Silber, Sigmund, Mau, Birgit, Leuner, Christian, Czyborra, Karen, Reuschling, Christina, Muno, Eva, Kleber, F., Rux, Sascha, Zeymer, U., Saad, Aly, Ibrahim, B. S. S., Elabady, Maged, Castro Beiras, A., Fernandez, Jorge Salgado, Navarro Del Arno, Felipe, Iniguez Romo, A., Cruz Fernandez, J. M., Mayoreal, Alejandro Recio, Rebanal, Franciso Javier Rivero, De La Borbolla, Mariano Garcia, Chaparro, Marinela, Brotons, C., Permanyer Miralda, C., Vilai Perez, Srta Irma, Moris, Cesar, Fernandez Aviles, F., De La Fuente Galan, Luis, Vinuela, Paula Tejedor, Malpartida De Torres, F., Mora, Javier, Rodriguez, Ignacio Santos, Bustamante, Itziar Piedra, Sanchez Fernandez, Pedro L., Diago Torrent, J. L., Diez Gil, Jose L., Perpinan, Javier, Palacios Motilla, V., Soledad Alcasena Juango, M., Berjon-Reyero, Jesus, Melgares Moreno, R., Guerrero, Juan Carlos Fernandez, Lehto, S., Savolainen, Kirsti, Nieminen, M. S., Syvanne, Mikko, Cohen-Solal, A., Oboa, Antoine-Sylvain, Bassand, J. P., Espinosa, Denis Pales, Jouet, Veronique, Montalescot, G., Gallois, Vanessa, Daubert, J. C., Clerc, Jean Michel, Machecourt, Jacques, Cottin, Y., Walker, D., Holland, Fhiona, Wood, D., Prosser, Jenni, Muir, Lis, Barber, Kate, Cleland, J. G. F., Cook, Jocelyn, Chapichadze, Zaza, Christos, Ioannis Skoularigisn Athanasiou, Tsiavou, Nastasia, Chrysohoou, Christina, Manginas, Athanassios, Terrovitis, John, Kanakakis, John, Vavuranakis, Manolis, Drakos, Stavros, Farmakis, Thomas, Samara, C., Papakosta, Christina, Bourantas, Christos, Michalis, L. K., Christos, Mpourantas, Foussas, Stefanos, Adamopoulou, Evdokia, Vardas, P. E., Marketou, Mary, Alotti, N., Basa, Anna Maria, Vigh, Andras, Preda, Istvan, Csoti, Eva, Keltai, M., Kerkovits, G., Hendler, Alberto, Blatt, Alex, Beyar, R., Shefer, Arie, Halon, David, Bentzvi, Margalait, Avramovitch, Naomi, Bakst, Avinoam, Cafri, Carlos, Grosbard, Aviva, Margolis, Bella, Suleiman, Khalid, Banai, Shmuel, Meerkin, David, Mosseri, Morris, Guita, Pnina, Jabara, Rifat, Jafari, Jamal, Ben Shitrit, Debi, Ghasan, null, Salameh, null, Brezins, Marc, Van Den Akker-Berman, Lily, Guetta, Victor, Rozenman, Yoseph, Biagini, A., Berti, Sergio, Ferrero, Massimo, Colombo, A., Roccaforte, R., Milici, Caterina, Scarpino, L., Salvi, A., Desideri, Alessandro, Sabbadin, Daniela, Galassi, Alfredo, Giuffrida, Giuseppe, Rognoni, Andrea, Vassanelli, Corrado, Paffoni, Paola, Cioppa, Angelo, Rubino, Paolo, De Carlo, Marco, Petronio, Anna Sonia, Naccarella, F., Saia, Francesco, Marzocchi, Antonio, Maranga, Stefano Sdringola, Presbitero, P., Valsecchi, Fazya, Piscione, Federico, Esposito, Giovanni, Santini, Napoli M., Tubaro, Marco, Erglis, A., Narbute, Inga, Kavoliuniene, Ausra, Zaliunas, R., Navickas, Ramunas, Grabauskiene, V., Luckute, Davia, Subkovas, Eduardas, Wagner, Daniel, Vermeer, F., Lousberg, Aimee, Fransen, Heidi, Breeman, Arno, Tebbe, Henriette, De Boer, M. J., Van Der Wal, Metske, Deckers, J., Vos, Jeroen, Leenders, C. M., Veerhoek, M. J., Jansen, Chris, Bijl, M., Koppelaar, Colinda, Van Den Linden, null, Brons, R., Widdershofen, J. W. M. G., Broers, Herman, Kontny, F., Jonzon, Marianne, Wodniecki, Jan, Tomasik, Andrzej, Trusz-Gluza, M., Nowak, Seweryn, Ruzyllo, Witold, Deptuch, Tomasz, Marques, Jorge, Matias, F., Madeira, H., Oliveira, Joaquim, Sargento, Luis, Ionac, Adina, Dragulescu, Iosif Stefan, Mut-Vitcu, Bogdan, Maximov, Daniela, Dorobantu, M., Apetrei, E., Niculescu, Rodica, Petrescu, Virgil, Bucsa, Adrian, Deleanu, Dan, Benedek, I. S., Hintea, Theodora, Aronov, D., Tikhomirova, Elena, Kranjec, I., Prokselj, Katja, Kanic, Vojko, Sepetoglu, Ahmet, Aytekin, S., Aytekin, V., Catakoglu, Alp Burak, Parlar, Hayri, Tufekcioglu, Suavi, Ozyedek, Zeki, Baltali, Mehmet, Kiziltan, null, Vukovic, Milan, Neskovic, A. N., Lenzen, M. J, Boersma, E, Bertrand, Me, Maier, W, Moris, C, Esposito, Giovanni, Piscione, Federico, Sechtem, U, Stahle, E, Widimsky, P, de Jaegere, P, Scholte op Reimer, W. J. M, Mercado, N, Wijns, W., University of Zurich, Wijns, W, Lenzen, M. J., Boersma, E., Bertrand, M. E., Maier, W., Moris, C., Piscione, F., Sechtem, U., Stahle, E., Widimsky, P., De Jaegere, P., Scholte Op Reimer, W. J. M., Mercado, N., Meier, B., Sergeant, P., Vos, J., Unger, F., Manini, Malika, Bramley, Claire, Laforest, Valérie, Taylor, Charle, Del Gaiso, Susan, Huber, Kurt, De Backer, Guy, Sirakova, Vera, Cerbak, Roman, Thayssen, Per, Lehto, Seppo, Blanc, Jean-Jacque, Delahaye, Françoi, Kobulia, Bondo, Zeymer, Uwe, Cokkinos, Denni, Karlocai, Kristof, Graham, Ian, Shelley, Emer, Behar, Shlomo, Maggioni, Aldo, Grabauskiene, Virginija, Deckers, Jaap, Asmussen, Inger, Stepinska, Janina, Gonçalves, Lino, Mareev, Vyacheslav, Riecansky, Igor, Kenda, Miran F., Alonso, Angele, Lopez-Sendon, José Lui, Rosengren, Annika, Buser, Peter, Okay, Tugrul, Sychov, Oleg, Fox, Kevin, Wood, David, Boersma, Eric, Crijns, Harry, Fox, Kim, Mcgregor, Keith, Mulder, Barbara, Priori, Sylvia, Rydén, Lar, Tavazzi, Luigi, Vahanian, Alec, Vardas, Pano, Wijns, William, Sarkisyan, Karine, Glogar, H. D., Derntl, Michael, Frick, Matthia, Pachinger, O., Zwick, Ralf, Vrints, Christiaan, Van Hertbruggen, El, Vercammen, Marc, Sysmans, Tineke, Schroeder, E., Domange, Juliette, De Pril, Hilde, De Vriese, Johan, Van Hecke, Tonny, Legrand, V., Gillon, Marie-France, Richardy, Michel, Doneux, P., Petrov, Ivo, Jorgova, J., Starcevic, Bori, Eeckhout, Eric, Berger, Alexandre, Prudent, Veronique, Camenzind, E., Masson, Nicola, Zambartas, Costa, Kleanthous, Helen, Widimsky, Petr, Stellova, Blanka, Aschermann, Michael, Simek, Stanislav, Kautzner, J., Karmazin, Vladimir, Svab, P., Indrak, Jan, Branny, M., Hladilova, Kveta, Kala, P., Thayssen, P., Cappelen, Helle, Jensen, Lisette Okkel, Gitt, A., Gehrke, Konstanze, Erbel, R., Gutersohn, Achim, Eggebrecht, Holger, Al Khani, Murad, Sechtem, Udo, Rosenberger, Antje, Vogelsberg, Holger, Klepzig, H., Schmidt, Arnold, Silber, Sigmund, Mau, Birgit, Leuner, Christian, Czyborra, Karen, Reuschling, Christina, Muno, Eva, Kleber, F., Rux, Sascha, Zeymer, U., Saad, Aly, Ibrahim, B. S. S., Elabady, Maged, Castro Beiras, A., Fernandez, Jorge Salgado, Navarro Del Arno, Felipe, Iniguez Romo, A., Cruz Fernandez, J. M., Mayoreal, Alejandro Recio, Rebanal, Franciso Javier Rivero, De La Borbolla, Mariano Garcia, Chaparro, Marinela, Brotons, C., Permanyer Miralda, C., Vilai Perez, Srta Irma, Moris, Cesar, Fernandez Aviles, F., De La Fuente Galan, Lui, Vinuela, Paula Tejedor, Malpartida De Torres, F., Mora, Javier, Rodriguez, Ignacio Santo, Bustamante, Itziar Piedra, Sanchez Fernandez, Pedro L., Diago Torrent, J. L., Diez Gil, Jose L., Perpinan, Javier, Palacios Motilla, V., Soledad Alcasena Juango, M., Berjon-Reyero, Jesu, Melgares Moreno, R., Guerrero, Juan Carlos Fernandez, Lehto, S., Savolainen, Kirsti, Nieminen, M. S., Syvanne, Mikko, Cohen-Solal, A., Oboa, Antoine-Sylvain, Bassand, J. P., Espinosa, Denis Pale, Jouet, Veronique, Montalescot, G., Gallois, Vanessa, Daubert, J. C., Clerc, Jean Michel, Machecourt, Jacque, Cottin, Y., Walker, D., Holland, Fhiona, Wood, D., Prosser, Jenni, Muir, Li, Barber, Kate, Cleland, J. G. F., Cook, Jocelyn, Chapichadze, Zaza, Christos, Ioannis Skoularigisn Athanasiou, Tsiavou, Nastasia, Chrysohoou, Christina, Manginas, Athanassio, Terrovitis, John, Kanakakis, John, Vavuranakis, Manoli, Drakos, Stavro, Farmakis, Thoma, Samara, C., Papakosta, Christina, Bourantas, Christo, Michalis, L. K., Christos, Mpouranta, Foussas, Stefano, Adamopoulou, Evdokia, Vardas, P. E., Marketou, Mary, Alotti, N., Basa, Anna Maria, Vigh, Andra, Preda, Istvan, Csoti, Eva, Keltai, M., Kerkovits, G., Hendler, Alberto, Blatt, Alex, Beyar, R., Shefer, Arie, Halon, David, Bentzvi, Margalait, Avramovitch, Naomi, Bakst, Avinoam, Cafri, Carlo, Grosbard, Aviva, Margolis, Bella, Suleiman, Khalid, Banai, Shmuel, Meerkin, David, Mosseri, Morri, Guita, Pnina, Jabara, Rifat, Jafari, Jamal, Ben Shitrit, Debi, Ghasan, Null, Salameh, Null, Brezins, Marc, Van Den Akker-Berman, Lily, Guetta, Victor, Rozenman, Yoseph, Biagini, A., Berti, Sergio, Ferrero, Massimo, Colombo, A., Roccaforte, R., Milici, Caterina, Scarpino, L., Salvi, A., Desideri, Alessandro, Sabbadin, Daniela, Galassi, Alfredo, Giuffrida, Giuseppe, Rognoni, Andrea, Vassanelli, Corrado, Paffoni, Paola, Cioppa, Angelo, Rubino, Paolo, De Carlo, Marco, Petronio, Anna Sonia, Naccarella, F., Saia, Francesco, Marzocchi, Antonio, Maranga, Stefano Sdringola, Presbitero, P., Valsecchi, Fazya, Santini, Napoli M., Tubaro, Marco, Erglis, A., Narbute, Inga, Kavoliuniene, Ausra, Zaliunas, R., Navickas, Ramuna, Grabauskiene, V., Luckute, Davia, Subkovas, Eduarda, Wagner, Daniel, Vermeer, F., Lousberg, Aimee, Fransen, Heidi, Breeman, Arno, Tebbe, Henriette, De Boer, M. J., Van Der Wal, Metske, Deckers, J., Vos, Jeroen, Leenders, C. M., Veerhoek, M. J., Jansen, Chri, Bijl, M., Koppelaar, Colinda, Van Den Linden, Null, Brons, R., Widdershofen, J. W. M. G., Broers, Herman, Kontny, F., Jonzon, Marianne, Wodniecki, Jan, Tomasik, Andrzej, Trusz-Gluza, M., Nowak, Seweryn, Ruzyllo, Witold, Deptuch, Tomasz, Marques, Jorge, Matias, F., Madeira, H., Oliveira, Joaquim, Sargento, Lui, Ionac, Adina, Dragulescu, Iosif Stefan, Mut-Vitcu, Bogdan, Maximov, Daniela, Dorobantu, M., Apetrei, E., Niculescu, Rodica, Petrescu, Virgil, Bucsa, Adrian, Deleanu, Dan, Benedek, I. S., Hintea, Theodora, Aronov, D., Tikhomirova, Elena, Kranjec, I., Prokselj, Katja, Kanic, Vojko, Sepetoglu, Ahmet, Aytekin, S., Aytekin, V., Catakoglu, Alp Burak, Parlar, Hayri, Tufekcioglu, Suavi, Ozyedek, Zeki, Baltali, Mehmet, Kiziltan, Null, Vukovic, Milan, Neskovic, A. N., Cardiology, Lenzen, Mj, and Scholte op Reimer, Wj

Subjects
Practice survey, Male, Coronary Stenosi, Coronary angiography, medicine.medical_treatment, Myocardial Infarction, Coronary Artery Disease, Angina, Coronary artery disease, Myocardial Revascularization, Stent, Myocardial infarction, Coronary Artery Bypass, Angioplasty, Balloon, Coronary, CABG, PCI, Professional Practice, Health Survey, Middle Aged, Europe, Treatment Outcome, Epidemiologic Method, Practice Guidelines as Topic, Cardiology, Stents, Female, Guideline Adherence, Cardiology and Cardiovascular Medicine, Human, medicine.medical_specialty, outcome, Euro Heart Survey, 610 Medicine & health, Platelet Glycoprotein GPIIb-IIIa Complex, 142-005 142-005, 2705 Cardiology and Cardiovascular Medicine, Angioplasty, Internal medicine, medicine, Humans, Angina, Unstable, cardiovascular diseases, Interventional cardiology, Unstable angina, business.industry, Coronary Artery Bypa, Coronary Stenosis, Percutaneous coronary intervention, Length of Stay, medicine.disease, Health Surveys, Conventional PCI, 570 Life sciences, biology, Epidemiologic Methods, business
Abstract

AIMS: The purpose of the Euro Heart Survey Programme of the European Society of Cardiology is to evaluate to which extent clinical practice endorses existing guidelines as well as to identify differences in population profiles, patient management, and outcome across Europe. The current survey focuses on the invasive diagnosis and treatment of patients with established coronary artery disease (CAD). METHODS AND RESULTS: Between November 2001 and March 2002, 7769 consecutive patients undergoing invasive evaluation at 130 hospitals (31 countries) were screened for the presence of one or more coronary stenosis >50% in diameter. Patient demographics and comorbidity, clinical presentation, invasive parameters, treatment options, and procedural techniques were prospectively entered in an electronic database (550 variables+29 per diseased coronary segment). Major adverse cardiac events (MACE) were evaluated at 30 days and 1 year. Out of 5619 patients with angiographically proven coronary stenosis (72% of screened population), 53% presented with stable angina while ST elevation myocardial infarction (STEMI) was the indication for coronary angiography in 16% and non-ST segment elevation myocardial infarction or unstable angina in 30%. Only medical therapy was continued in 21%, whereas mechanical revascularization was performed in the remainder [percutaneous coronary intervention (PCI) in 58% and coronary artery bypass grafting (CABG) in 21%]. Patients referred for PCI were younger, were more active, had a lower risk profile, and had less comorbid conditions. CABG was performed mostly in patients with left main lesions (21%), two- (25%), or three-vessel disease (67%) with 4.1 diseased segments, on average. Single-vessel PCI was performed in 82% of patients with either single- (45%), two- (33%), or three-vessel disease (21%). Stents were used in 75% of attempted lesions, with a large variation between sites. Direct PCI for STEMI was performed in 410 cases, representing 7% of the entire workload in the participating catheterization laboratories. Time delay was within 90 min in 76% of direct PCI cases. In keeping with the recommendations of practice guidelines, the survey identified under-use of adjunctive medication (GP IIb/IIIa receptor blockers, statins, and angiotensin-converting enzyme-inhibitors). Mortality rates at 30 days and 1 year were low in all subgroups. MACE primarily consisted of repeat PCI (12%). CONCLUSION: The current Euro Heart Survey on coronary revascularization was performed in the era of bare metal stenting and provides a global European picture of the invasive approach to patients with CAD. These data will serve as a benchmark for the future evaluation of the impact of drug-eluting stents on the practice of interventional cardiology and bypass surgery.

Published
2005

2. Depression influences the quality of diabetes-related self-management activities in elderly patients with type 2 diabetes: a cross-sectional study

Author

Cristian Oancea, Bogdan Timar, Gabriela Mut-Vitcu, Ioan Cosmin Citu, and Romulus Timar

Subjects
Male, medicine.medical_specialty, Cross-sectional study, media_common.quotation_subject, 030209 endocrinology & metabolism, Type 2 diabetes, Severity of Illness Index, Diabetes Complications, 03 medical and health sciences, 0302 clinical medicine, Quality of life (healthcare), Diabetes mellitus, Surveys and Questionnaires, self-care, Medicine, Humans, Quality (business), 030212 general & internal medicine, Exercise, Depression (differential diagnoses), media_common, Aged, Original Research, Aged, 80 and over, Psychiatric Status Rating Scales, Self-management, diabetes, business.industry, Depression, Romania, General Medicine, Middle Aged, medicine.disease, Self Care, Cross-Sectional Studies, Logistic Models, Diabetes Mellitus, Type 2, quality of life, Clinical Interventions in Aging, Multivariate Analysis, Self care, Physical therapy, Female, Geriatrics and Gerontology, business
Abstract

Gabriela Mut-Vitcu,1 Bogdan Timar,2 Romulus Timar,1 Cristian Oancea,3 Ioan Cosmin Citu4 1Second Department of Internal Medicine, 2Department of Functional Sciences, 3Department of Infectious Diseases, 4Department of Obstetrics and Gynecology, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania Purpose: To evaluate the prevalence of depression and its impact on the quality of diabetes-related self-care activities in elderly patients with type 2 diabetes. Patients and methods: In this cross-sectional study, 184 patients with type 2 diabetes were enrolled. Depression was evaluated using Patient Health Questionnaire-9 while the quality of diabetes-related self-care activities was assessed using the Summary of Diabetes-Related Self Care Activities Questionnaire. Results: In our study group, 53.3% of the patients had moderate depression, 17.9% had severe depression, and 28.8% had no depression symptoms. Patient’s age (P=0.024), presence of diabetic neuropathy (P

Published
2016

3. Whole-Body Distribution and Radiation Dosimetry of 11C-(+)-PHNO, a D2/3 Agonist Ligand

Author

Alvina Ng, Alan A. Wilson, Peter M. Bloomfield, Pablo Rusjan, Romina Mizrahi, Irina Vitcu, and Sylvain Houle

Subjects
Adult, Male, Agonist, Adult male, medicine.drug_class, Radiation, Ligands, Effective dose (radiation), Oxazines, medicine, Humans, Dosimetry, Tissue Distribution, Radiology, Nuclear Medicine and imaging, Radiometry, Receptors, Dopamine D2, business.industry, Receptors, Dopamine D3, Healthy subjects, Internal radiation, Organ Size, Positron-Emission Tomography, Dopamine Agonists, Female, Whole body, Nuclear medicine, business
Abstract

Using PET, we measured the whole-body distribution of 11C-(+)-PHNO (11C-(+)-4-propyl-9-hydroxynaphthoxazine), a D2/3 agonist, as a function of time in adult subjects in order to determine the internal radiation dose. Methods: PET whole-body data were acquired after the injection of 11C-(+)-PHNO (∼360 MBq) in 6 healthy subjects (3 male and 3 female). The PET acquisition duration was a maximum of 112.5 min, and 9 discrete time frames were obtained. After reconstruction of the emission data, 6 organs were identified in the images as exhibiting uptake above background levels. Regions of interest were delineated on these organs, and time–activity curves were generated. The time–activity curve data were corrected for the injected activity, specific organ density, and volume, from which normalized accumulated activities (previously known as residence times) were calculated. The normalized accumulated activities were then used with the software code OLINDA/EXM 1.1 to calculate the internal doses for the standard adult male and female models. Results: The mean effective dose was estimated to be 4.5 ± 0.3 μSv/MBq when all subjects were included and the male model was applied for the dosimetry calculation, and the mean effective dose was estimated to be 5.2 ± 0.2 μSv/MBq when the females were considered separately and the female model was applied for the calculation. The organ receiving the highest dose was the liver (17.9 ± 3.9 μSv/MBq), followed by the kidneys (14.3 ± 3.6 μSv/MBq) and the urinary bladder wall (13.5 ± 3.7 μSv/MBq). Conclusion: The estimated radiation doses for 11C-(+)-PHNO are similar to those reported for other radiotracers labeled with 11C. 11C-(+)-PHNO may be used for multiple PET scans in the same subject and remain within regulatory guidelines.

Published
2012

4. Quantitation of Translocator Protein Binding in Human Brain with the Novel Radioligand [18F]-FEPPA and Positron Emission Tomography

Author

Peter M. Bloomfield, Pablo Rusjan, Irina Vitcu, Romina Mizrahi, Jeffrey H. Meyer, Sylvain Houle, and Alan A. Wilson

Subjects
Adult, Male, Fluorine Radioisotopes, Pyridines, Coefficient of variation, Young Adult, Translocator protein, medicine, Radioligand, Humans, Anilides, Aged, biology, medicine.diagnostic_test, business.industry, Chemistry, Outcome measures, Brain, Binding potential, Human brain, Middle Aged, medicine.anatomical_structure, Neurology, Positron emission tomography, Positron-Emission Tomography, biology.protein, Original Article, Female, Neurology (clinical), Tomography, Radiopharmaceuticals, Cardiology and Cardiovascular Medicine, Nuclear medicine, business, Protein Binding
Abstract

This article describes the kinetic modeling of [18F]-FEPPA binding to translocator protein 18 kDa in the human brain using high-resolution research tomograph (HRRT) positron emission tomography. Positron emission tomography scans were performed in 12 healthy volunteers for 180 minutes. A two-tissue compartment model (2-CM) provided, with no exception, better fits to the data than a one-tissue model. Estimates of total distribution volume ( VT), specific distribution volume ( VS), and binding potential ( BPND) demonstrated very good identifiability (based on coefficient of variation ( COV)) for all the regions of interest (ROIs) in the gray matter ( COV VT < 7%, COV VS < 8%, COV BPND < 11%). Reduction of the length of the scan to 2 hours is feasible as VS and VT showed only a small bias (6% and 7.5%, respectively). Monte Carlo simulations showed that, even under conditions of a 500% increase in specific binding, the identifiability of VT and VS was still very good with COVT values obtained from an unconstrained 2-CM with data from a 2-hour scan support the use of VT as an appropriate and feasible outcome measure for [18F]-FEPPA.

Published
2011

5. Brain region binding of the D2/3 agonist [11C]-(+)-PHNO and the D2/3 antagonist [11C]raclopride in healthy humans

Author

Philip Seeman, Irina Vitcu, Pablo Rusjan, Romina Mizrahi, David C. Mamo, Shitij Kapur, Ariel Graff-Guerrero, Nathalie Ginovart, Alan A. Wilson, and Matthaeus Willeit

Subjects
Male, Time Factors, Dopamine, Striatum, ddc:616.89, Substantia Nigra/diagnostic imaging/metabolism, Basal ganglia, Radioligand, Tissue Distribution, Carbon Radioisotopes, Receptors, Dopamine D2/agonists/metabolism, Research Articles, Raclopride, Brain Mapping, Dopamine Agonists/metabolism/pharmacokinetics, Radiological and Ultrasound Technology, Chemistry, Putamen, Substantia Nigra, Dopamine D2 Receptor Antagonists, Globus pallidus, Neurology, Dopamine Agonists, Female, Anatomy, medicine.drug, Adult, Agonist, medicine.medical_specialty, Raclopride/metabolism/pharmacokinetics, medicine.drug_class, Globus Pallidus, Binding, Competitive, Binding, Competitive/drug effects/physiology, Internal medicine, Brain Mapping/methods, Oxazines, medicine, Humans, Radiology, Nuclear Medicine and imaging, Corpus Striatum/diagnostic imaging/metabolism, Globus Pallidus/diagnostic imaging/metabolism, Neostriatum/diagnostic imaging/metabolism, Receptors, Dopamine D2, Antagonist, Positron-Emission Tomography/methods, Dopamine Antagonists/metabolism/pharmacokinetics, Corpus Striatum, Dopamine/metabolism, Neostriatum, Endocrinology, nervous system, Positron-Emission Tomography, Dopamine Antagonists, Oxazines/metabolism/pharmacokinetics, Neurology (clinical), Neuroscience
Abstract

The D(2) receptors exist in either the high‐ or low‐affinity state with respect to agonists, and while agonists bind preferentially to the high‐affinity state, antagonists do not distinguish between the two states. [(11)C]‐(+)‐PHNO is a PET D(2) agonist radioligand and therefore provides a preferential measure of the D(2) (high) receptors. In contrast, [(11)C]raclopride is an antagonist radioligand and thus binds with equal affinity to the D(2) high‐ and low‐affinity states. The aim was to compare the brain uptake, distribution and binding characteristics between [(11)C]‐(+)‐PHNO and [(11)C]raclopride in volunteers using a within‐subject design. Both radioligands accumulated in brain areas rich in D(2)/D(3)‐receptors. However, [(11)C]‐(+)‐PHNO showed preferential uptake in the ventral striatum and globus pallidus, while [(11)C]raclopride showed preferential uptake in the dorsal striatum. Mean binding potentials were higher in the putamen (4.3 vs. 2.8) and caudate (3.4 vs 2.1) for [(11)C]raclopride, equal in the ventral‐striatum (3.4 vs. 3.3), and higher in the globus pallidus for [(11)C]‐(+)‐PHNO (1.8 vs. 3.3). Moreover [(11)C]‐(+)‐PHNO kinetics in the globus pallidus showed a slower washout than other regions. One explanation for the preferential binding of [(11)C]‐(+)‐PHNO in the globus pallidus and ventral‐striatum could be the presence of a greater proportion of high‐ vs. low‐affinity receptors in these areas. Alternatively, the observed distribution could also be explained by a preferential binding of D(3)‐over‐D(2) with [(11)C]‐(+)‐PHNO. This differential binding of agonist vs. antagonist radioligand, especially in the critically important region of the limbic striatum/pallidum, offers new avenues to investigate the role of the dopamine system in health and disease. Hum Brain Mapp 2008. © 2007 Wiley‐Liss, Inc.

Published
2008

6. Separate brain regions code for salience vs. valence during reward prediction in humans

Author

Irina Vitcu, Shitij Kapur, Jimmy Jensen, Adrian P. Crawley, Matthäus Willeit, David J. Mikulis, and Andrew J. A. Smith

Subjects
Adult, Male, Conditioning, Classical, Models, Neurological, Choice Behavior, Brain mapping, Basal Ganglia, Reward, Salience (neuroscience), Basal ganglia, Avoidance Learning, medicine, Humans, Radiology, Nuclear Medicine and imaging, Valence (psychology), Research Articles, Brain Mapping, Radiological and Ultrasound Technology, Ventral striatum, Magnetic Resonance Imaging, medicine.anatomical_structure, nervous system, Neurology, Incentive salience, Female, Orbitofrontal cortex, Neurology (clinical), Anatomy, Aversive Stimulus, Psychology, Neuroscience
Abstract

Predicting rewards and avoiding aversive conditions is essential for survival. Recent studies using computational models of reward prediction implicate the ventral striatum in appetitive rewards. Whether the same system mediates an organism's response to aversive conditions is unclear. We examined the question using fMRI blood oxygen level‐dependent measurements while healthy volunteers were conditioned using appetitive and aversive stimuli. The temporal difference learning algorithm was used to estimate reward prediction error. Activations in the ventral striatum were robustly correlated with prediction error, regardless of the valence of the stimuli, suggesting that the ventral striatum processes salience prediction error. In contrast, the orbitofrontal cortex and anterior insula coded for the differential valence of appetitive/aversive stimuli. Given its location at the interface of limbic and motor regions, the ventral striatum may be critical in learning about motivationally salient stimuli, regardless of valence, and using that information to bias selection of actions. Inc. Hum Brain Mapp, 2007. © 2006 Wiley‐Liss, Inc.

Published
2007

7. Whole-body radiation dosimetry of 11C-carbonyl-URB694: a PET tracer for fatty acid amide hydrolase

Author

Junchao Tong, Irina Vitcu, Pablo Rusjan, Romina Mizrahi, Isabelle Boileau, Alan A. Wilson, Asfandyar Mufti, Stephen J. Kish, Sylvain Houle, and Peter M. Bloomfield

Subjects
Adult, Male, Amidohydrolases, Image Processing, Computer-Assisted, Medicine, Humans, Radiology, Nuclear Medicine and imaging, In patient, Tissue Distribution, Whole Body Imaging, Prospective Studies, Pet tracer, Radiometry, Public Facility, Border crossing, business.industry, Biphenyl Compounds, Middle Aged, medicine.disease, Positron-Emission Tomography, Female, Medical emergency, Carbamates, Radiopharmaceuticals, Nuclear medicine, business, Whole body, Whole-Body Irradiation
Abstract

1993 Objectives To determine by a national survey: 1) the frequency of detection by public screening facilities of radioactivity in patients (pts) who had been treated with 131I for differentiated thyroid cancer (DTC), 2) the types and frequency of the various public facilities where pts were detected, and 3) the management of these pts by the security personnel. Methods Data were tabulated from a Thyroid Cancer Survivors Association, Inc. (ThyCa) website survey from November 2013 to December 2013 and was emailed to ~30,000 associates of ThyCa. Answers were tabulated of respondents (rpds) who reported that s/he 1) was >18 yo, 2) had at least one tx of 131I, and 3) was responding for his/her last 131I tx. The study was approved by the IRB. Results Of 334 rpds, 6.9% (23) attempted to pass through a public facility security checkpoint. Of these 23 pts all were detected and the detections occurred in an airport (7), border crossing (7), government building (3), shopping mall (3), train station (2), and steel recycling plant (1). The security personnel questioned 19 rpds, released 14 rpds without change in travel plans, rescanned 9 rpds, released 1 rpd with change in travel plans, and denied passage in 1 rpd. Security personnel verified the rpd’s 131I tx by examining an official document from the treating physician that was provided by 14 rpds, calling the treating facility regarding 3 rspds, and operating radiation detectors to identify the type and source of radiation in 2 rspds. Security personnel did not verify 131I tx in 4 rspds. Conclusions Public detection of radioactivity after 131I tx is infrequent, occurring in only 6.9% of respondents. Although airports and border crossings accounted for 61% of the sites of detection, the number of detected respondents was very low, and further respondents of the survey continue to be collected.

Published
2014

8. The additional value of patient-reported health status in predicting 1-year mortality after invasive coronary procedures: a report from the Euro Heart Survey on Coronary Revascularisation

Author

Lenzen M. J., Scholte Op Reimer W. J. M., Pedersen S. S., Boersma E., Maier W., Widimsky P., Simoons M. L., Mercado N. F., Wijns W., Bertrand M., Meier B., Sechtem U., Sergeant P., Stahle E., Unger F., Manini M., Bramley C., Laforest V., Taylor C., Del Gaiso S., Huber K., De Backer G., Sirakova V., Cerbak R., Thayssen P., Lehto S., Blanc J. -J., Delahaye F., Kobulia B., Zeymer U., Cokkinos D., Karlocai K., Graham I., Shelley E., Behar S., Maggioni A., Grabauskiene V., Deckers J., Asmussen I., Stepinska J., Goncalves L., Mareev V., Riecansky I., Kenda M. F., Alonso A., Lopez-Sendon J. L., Rosengren A., Buser P., Okay T., Sychov O., Fox K., Wood D., Crijns H., McGregor K., Mulder B., Priori S., Ryden L., Tavazzi L., Vahanian A., Vardas P., Sarkisyan K., Glogar H. D., Frick M., Pachinger O., Zwick R., Vrints C., Van Hertbruggen E., Vercammen M., Sysmans T., Schroeder E., Domange J., De Pril H., De Vriese J., Van Hecke T., Legrand V., Gillon M. -F., Richardy M., Doneux P., Petrov I., Jorgova J., Starcevic B., Eeckhout E., Berger A., Prudent V., Camenzind E., Masson N., Zambartas C., Kleanthous H., Stellova B., Aschermann M., Simek S., Kautzner J., Karmazin V., Svab P., Indrak J., Branny M., Hladilova K., Kala P., Cappelen H., Jensen L. O., Gitt A., Gehrke K., am Rhein L., Erbel R., Gutersohn A., Eggebrecht H., Al Khani M., Rosenberger A., Vogelsberg H., Klepzig H., Schmidt A., Silber S., Mau B., Leuner C., Czyborra K., Reuschling C., Muno E., Nauheim B., Kleber F., Rux S., Saad A., Elabady M., Beiras A. C., Fernandez J. S., del Arno F. N., Romo A. I., Fernandez J. M. C., Mayoreal A. R., Rebanal F. J. R., de la Borbolla M. G., Chaparro M., Brotons C., Miralda C. P., Vila i Perez S. I., Moris C., Aviles F. F., de la Fuente Galan L., Vinuela P. T., de Torres F. M., Mora J., Rodriguez I. S., Bustamante I. P., Fernandez P. L. S., Torrent J. L. D., Diez Gil J. L., Perpinan J., Motilla V. P., Juango M. S. A., Berjon-Reyero J., Moreno R. M., Guerrero J. C. F., Savolainen K., Syvanne M., Cohen-Solal A., Oboa A. -S., Bassand J. P., Espinosa D. P., Jouet V., Cedex B., Montalescot G., Gallois V., Daubert J. C., Clerc J. M., Machecourt J., Cottin Y., Walker D., Holland F., Prosser J., Muir L., Barber K., Cleland J. G. F., Cook J., Chapichadze Z., Christos I. S. A., Tsiavou N., Chrysohoou C., Manginas A., Terrovitis J., Kanakakis J., Vavuranakis M., Drakos S., Farmakis T., Samara C., Papakosta C., Bourantas C., Michalis L. K., Christos M., Foussas S., Adamopoulou E., Vardas P. E., Marketou M., Alotti N., Basa A. M., Vigh A., Preda I., Csoti E., Keltai M., Kerkovits G., Hendler A., Blatt A., Yakov B., Beyar R., Shefer A., Halon D., Bentzvi M., Avramovitch N., Bakst A., Saba K., Cafri C., Grosbard A., Sheva B., Margolis B., Suleiman K., Banai S., Meerkin D., Mosseri M., Guita P., Jabara R., Jafari J., Shitrit D. B., Ghasan Salameh, Brezins M., van den Akker-Berman L., Guetta V., Hashomer T., Rozenman Y., Biagini A., Berti S., Ferrero M., Colombo A., Roccaforte R., Milici C., Scarpino L., Salvi A., Desideri A., Sabbadin D., Veneto C., Galassi A., Giuffrida G., Rognoni A., Vassanelli C., Paffoni P., Cioppa A., Rubino P., de Carlo M., Petronio A. S., Naccarella F., Saia F., Marzocchi A., Maranga S. S., Presbitero P., Valsecchi F., Piscione F., Esposito G., Santini N. M., Tubaro M., Erglis A., Narbute I., Kavoliuniene A., Zaliunas R., Navickas R., Luckute D., Subkovas E., Wagner D., Vermeer F., Lousberg A., Fransen H., Breeman A., Tebbe H., De Boer M. J., van der Wal M., Vos J., Leenders C. M., Veerhoek M. J., Jansen C., Bijl M., Koppelaar C., den Linden V., Brons R., Widdershofen J. W. M. G., Broers H., Kontny F., Jonzon M., Wodniecki J., Tomasik A., Trusz-Gluza M., Nowak S., Ruzyllo W., Deptuch T., Marques J., Matias F., Madeira H., Oliveira J., Sargento L., Ionac A., Dragulescu I. S., Mut-Vitcu B., Maximov D., Dorobantu M., Apetrei E., Niculescu R., Petrescu V., Bucsa A., Deleanu D., Bucharest, Benedek I. S., Hintea T., Aronov D., Tikhomirova E., Kranjec I., Prokselj K., Kanic V., Sepetoglu A., Aytekin S., Aytekin V., Catakoglu A. B., Parlar H., Tufekcioglu S., Ozyedek Z., Baltali M., Kiziltan D., Vukovic M., Neskovic A. N., Cardiology, Lenzen, M. J., Scholte Op Reimer, W. J. M., Pedersen, S. S., Boersma, E., Maier, W., Widimsky, P., Simoons, M. L., Mercado, N. F., Wijns, W., Bertrand, M., Meier, B., Sechtem, U., Sergeant, P., Stahle, E., Unger, F., Manini, M., Bramley, C., Laforest, V., Taylor, C., Del Gaiso, S., Huber, K., De Backer, G., Sirakova, V., Cerbak, R., Thayssen, P., Lehto, S., Blanc, J. -J., Delahaye, F., Kobulia, B., Zeymer, U., Cokkinos, D., Karlocai, K., Graham, I., Shelley, E., Behar, S., Maggioni, A., Grabauskiene, V., Deckers, J., Asmussen, I., Stepinska, J., Goncalves, L., Mareev, V., Riecansky, I., Kenda, M. F., Alonso, A., Lopez-Sendon, J. L., Rosengren, A., Buser, P., Okay, T., Sychov, O., Fox, K., Wood, D., Crijns, H., Mcgregor, K., Mulder, B., Priori, S., Ryden, L., Tavazzi, L., Vahanian, A., Vardas, P., Sarkisyan, K., Glogar, H. D., Frick, M., Pachinger, O., Zwick, R., Vrints, C., Van Hertbruggen, E., Vercammen, M., Sysmans, T., Schroeder, E., Domange, J., De Pril, H., De Vriese, J., Van Hecke, T., Legrand, V., Gillon, M. -F., Richardy, M., Doneux, P., Petrov, I., Jorgova, J., Starcevic, B., Eeckhout, E., Berger, A., Prudent, V., Camenzind, E., Masson, N., Zambartas, C., Kleanthous, H., Stellova, B., Aschermann, M., Simek, S., Kautzner, J., Karmazin, V., Svab, P., Indrak, J., Branny, M., Hladilova, K., Kala, P., Cappelen, H., Jensen, L. O., Gitt, A., Gehrke, K., am Rhein, L., Erbel, R., Gutersohn, A., Eggebrecht, H., Al Khani, M., Rosenberger, A., Vogelsberg, H., Klepzig, H., Schmidt, A., Silber, S., Mau, B., Leuner, C., Czyborra, K., Reuschling, C., Muno, E., Nauheim, B., Kleber, F., Rux, S., Saad, A., Elabady, M., Beiras, A. C., Fernandez, J. S., del Arno, F. N., Romo, A. I., Fernandez, J. M. C., Mayoreal, A. R., Rebanal, F. J. R., de la Borbolla, M. G., Chaparro, M., Brotons, C., Miralda, C. P., Vila i Perez, S. I., Moris, C., Aviles, F. F., de la Fuente Galan, L., Vinuela, P. T., de Torres, F. M., Mora, J., Rodriguez, I. S., Bustamante, I. P., Fernandez, P. L. S., Torrent, J. L. D., Diez Gil, J. L., Perpinan, J., Motilla, V. P., Juango, M. S. A., Berjon-Reyero, J., Moreno, R. M., Guerrero, J. C. F., Savolainen, K., Syvanne, M., Cohen-Solal, A., Oboa, A. -S., Bassand, J. P., Espinosa, D. P., Jouet, V., Cedex, B., Montalescot, G., Gallois, V., Daubert, J. C., Clerc, J. M., Machecourt, J., Cottin, Y., Walker, D., Holland, F., Prosser, J., Muir, L., Barber, K., Cleland, J. G. F., Cook, J., Chapichadze, Z., Christos, I. S. A., Tsiavou, N., Chrysohoou, C., Manginas, A., Terrovitis, J., Kanakakis, J., Vavuranakis, M., Drakos, S., Farmakis, T., Samara, C., Papakosta, C., Bourantas, C., Michalis, L. K., Christos, M., Foussas, S., Adamopoulou, E., Vardas, P. E., Marketou, M., Alotti, N., Basa, A. M., Vigh, A., Preda, I., Csoti, E., Keltai, M., Kerkovits, G., Hendler, A., Blatt, A., Yakov, B., Beyar, R., Shefer, A., Halon, D., Bentzvi, M., Avramovitch, N., Bakst, A., Saba, K., Cafri, C., Grosbard, A., Sheva, B., Margolis, B., Suleiman, K., Banai, S., Meerkin, D., Mosseri, M., Guita, P., Jabara, R., Jafari, J., Shitrit, D. B., Ghasan, Salameh, Brezins, M., van den Akker-Berman, L., Guetta, V., Hashomer, T., Rozenman, Y., Biagini, A., Berti, S., Ferrero, M., Colombo, A., Roccaforte, R., Milici, C., Scarpino, L., Salvi, A., Desideri, A., Sabbadin, D., Veneto, C., Galassi, A., Giuffrida, G., Rognoni, A., Vassanelli, C., Paffoni, P., Cioppa, A., Rubino, P., de Carlo, M., Petronio, A. S., Naccarella, F., Saia, F., Marzocchi, A., Maranga, S. S., Presbitero, P., Valsecchi, F., Piscione, F., Esposito, G., Santini, N. M., Tubaro, M., Erglis, A., Narbute, I., Kavoliuniene, A., Zaliunas, R., Navickas, R., Luckute, D., Subkovas, E., Wagner, D., Vermeer, F., Lousberg, A., Fransen, H., Breeman, A., Tebbe, H., De Boer, M. J., van der Wal, M., Vos, J., Leenders, C. M., Veerhoek, M. J., Jansen, C., Bijl, M., Koppelaar, C., den Linden, V., Brons, R., Widdershofen, J. W. M. G., Broers, H., Kontny, F., Jonzon, M., Wodniecki, J., Tomasik, A., Trusz-Gluza, M., Nowak, S., Ruzyllo, W., Deptuch, T., Marques, J., Matias, F., Madeira, H., Oliveira, J., Sargento, L., Ionac, A., Dragulescu, I. S., Mut-Vitcu, B., Maximov, D., Dorobantu, M., Apetrei, E., Niculescu, R., Petrescu, V., Bucsa, A., Deleanu, D., Bucharest, Benedek, I. S., Hintea, T., Aronov, D., Tikhomirova, E., Kranjec, I., Prokselj, K., Kanic, V., Sepetoglu, A., Aytekin, S., Aytekin, V., Catakoglu, A. B., Parlar, H., Tufekcioglu, S., Ozyedek, Z., Baltali, M., Kiziltan, D., Vukovic, M., and Neskovic, A. N.

Subjects
Male, medicine.medical_specialty, Epidemiology, medicine.medical_treatment, Health Status, Coronary Artery Disease, Revascularization, Coronary artery disease, Cohort Studies, Risk Factors, Surveys and Questionnaires, medicine, Myocardial Revascularization, Surveys and Questionnaire, Humans, Prospective Studies, Prospective cohort study, Aged, business.industry, Risk Factor, Mortality rate, Confounding, Middle Aged, medicine.disease, Surgery, Europe, Prospective Studie, Treatment Outcome, Emergency medicine, Population study, Female, Cohort Studie, Cardiology and Cardiovascular Medicine, business, Human, Cohort study
Abstract

Objective: Self-perceived health status may be helpful in identifying patients at high risk for adverse outcomes. The Euro Heart Survey on Coronary Revascularization (EHS-CR) provided an opportunity to explore whether impaired health status was a predictor of 1-year mortality in patients with coronary artery disease (CAD) undergoing angiographic procedures. Methods: Data from the EHS-CR that included 5619 patients from 31 member countries of the European Society of Cardiology were used. Inclusion criteria for the current study were completion of a self-report measure of health status, the EuroQol Questionnaire (EQ-5D) at discharge and information on 1-year follow-up, resulting in a study population of 3786 patients. Results: The 1-year mortality was 3.2% (n = 120). Survivors reported fewer problems on the five dimensions of the EQ-5D as compared with non-survivors. A broad range of potential confounders were adjusted for, which reached a p

Published
2006

9. Patients enrolled in coronary intervention trials are not representative of patients in clinical practice: results from the Euro Heart Survey on Coronary Revascularization

Author

Hordijk-Trion M., Lenzen M., Wijns W., De Jaegere P., Simoons M. L., Scholte Op Reimer W. J. M., Bertrand M. E., Mercado N., Boersma E., Maier W., Meier B., Moris C., Piscione F., Sechtem U., Sergeant P., Stahle E., Vos J., Widimsky P., Unger F., Manini M., Bramley C., Laforest V., Taylor C., Del Gaiso S., Huber K., De Backer G., Sirakova V., Cerbak R., Thayssen P., Lehto S., Blanc J. -J., Delahaye F., Kobulia B., Zeymer U., Cokkinos D., Karlocai K., Graham I., Shelley E., Behar S., Maggioni A., Grabauskiene V., Deckers J., Asmussen I., Stepinska J., Goncalves L., Mareev V., Riecansky I., Kenda M. F., Alonso A., Lopez-Sendon J. L., Rosengren A., Buser P., Okay T., Sychov O., Fox K., Wood D., Crijns H., McGregor K., Mulder B., Priori S., Ryden L., Tavazzi L., Vahanian A., Vardas P., Sarkisyan K., Glogar H. D., Frick M., Pachinger O., Zwick R., Vrints C., Van Hertbruggen E., Vercammen M., Sysmans T., Schroeder E., Domange J., De Pril H., De Vriese J., Van Hecke T., Legrand V., Gillon M. -F., Richardy M., Doneux P., Petrov I., Jorgova J., Starcevic B., Eeckhout E., Berger A., Prudent V., Camenzind E., Masson N., Zambartas C., Kleanthous H., Stellova B., Aschermann M., Simek S., Kautzner J., Karmazin V., Svab P., Indrak J., Branny M., Hladilova K., Kala P., Cappelen H., Jensen L. O., Gitt A., Gehrke K., am Rhein L., Erbel R., Gutersohn A., Eggebrecht H., Al Khani M., Rosenberger A., Vogelsberg H., Klepzig H., Schmidt A., Silber S., Mau B., Leuner C., Czyborra K., Reuschling C., Muno E., Nauheim B., Kleber F., Rux S., Saad A., Elabady M., Beiras A. C., Fernandez J. S., del Arno F. N., Romo A. I., Fernandez J. M. C., Mayoreal A. R., Rebanal F. J. R., de la Borbolla M. G., Chaparro M., Brotons C., Miralda C. P., Vila i Perez S. I., Aviles F. F., de la Fuente Galan L., Vinuela P. T., de Torres F. M., Mora J., Rodriguez I. S., Bustamante I. P., Fernandez P. L. S., Torrent J. L. D., Gil J. L. D., Perpinan J., Motilla V. P., Juango M. S. A., Berjon-Reyero J., Moreno R. M., Guerrero J. C. F., Savolainen K., Syvanne M., Cohen-Solal A., Oboa A. -S., Bassand J. P., Espinosa D. P., Jouet V., Cedex B., Montalescot G., Gallois V., Daubert J. C., Clerc J. M., Machecourt J., Cottin Y., Walker D., Holland F., Prosser J., Muir L., Barber K., Cleland J. G. F., Cook J., Chapichadze Z., Christos I. S. A., Tsiavou N., Chrysohoou C., Manginas A., Terrovitis J., Kanakakis J., Vavuranakis M., Drakos S., Farmakis T., Samara C., Papakosta C., Bourantas C., Michalis L. K., Christos M., Foussas S., Adamopoulou E., Marketou M., Alotti N., Basa A. M., Vigh A., Preda I., Csoti E., Keltai M., Kerkovits G., Hendler A., Blatt A., Yakov B., Beyar R., Shefer A., Halon D., Bentzvi M., Avramovitch N., Bakst A., Saba K., Cafri C., Grosbard A., Sheva B., Margolis B., Suleiman K., Banai S., Meerkin D., Mosseri M., Guita P., Jabara R., Jafari J., Shitrit D. B., Ghasan D., Salameh D., Brezins M., van den Akker-Berman L., Guetta V., Hashomer T., Rozenman Y., Biagini A., Berti S., Ferrero M., Colombo A., Roccaforte R., Milici C., Scarpino L., Salvi A., Desideri A., Sabbadin D., Veneto C., Galassi A., Giuffrida G., Rognoni A., Vassanelli C., Paffoni P., Cioppa A., Rubino P., de Carlo M., Petronio A. S., Naccarella F., Saia F., Marzocchi A., Maranga S. S., Presbitero P., Valsecchi F., Esposito G., Santini N. M., Tubaro M., Erglis A., Narbute I., Kavoliuniene A., Zaliunas R., Navickas R., Luckute D., Subkovas E., Wagner D., Vermeer F., Lousberg A., Fransen H., Breeman A., Tebbe H., De Boer M. J., van der Wal M., Leenders C. M., Veerhoek M. J., Jansen C., Bijl M., Koppelaar C., den Linden V., Brons R., Widdershofen J. W. M. G., Broers H., Kontny F., Jonzon M., Wodniecki J., Tomasik A., Trusz-Gluza M., Nowak S., Ruzyllo W., Deptuch T., Marques J., Matias F., Madeira H., Oliveira J., Sargento L., Ionac A., Dragulescu I. S., Mut-Vitcu B., Maximov D., Dorobantu M., Apetrei E., Niculescu R., Petrescu V., Bucsa A., Deleanu D., Bucharest, Benedek I. S., Hintea T., Aronov D., Tikhomirova E., Kranjec I., Prokselj K., Kanic V., Sepetoglu A., Aytekin S., Aytekin V., Catakoglu A. B., Parlar H., Tufekcioglu S., Ozyedek Z., Baltali M., Kiziltan, Vukovic M., Neskovic A. N., Cardiology, Hordijk-Trion, M., Lenzen, M., Wijns, W., De Jaegere, P., Simoons, M. L., Scholte Op Reimer, W. J. M., Bertrand, M. E., Mercado, N., Boersma, E., Maier, W., Meier, B., Moris, C., Piscione, F., Sechtem, U., Sergeant, P., Stahle, E., Vos, J., Widimsky, P., Unger, F., Manini, M., Bramley, C., Laforest, V., Taylor, C., Del Gaiso, S., Huber, K., De Backer, G., Sirakova, V., Cerbak, R., Thayssen, P., Lehto, S., Blanc, J. -J., Delahaye, F., Kobulia, B., Zeymer, U., Cokkinos, D., Karlocai, K., Graham, I., Shelley, E., Behar, S., Maggioni, A., Grabauskiene, V., Deckers, J., Asmussen, I., Stepinska, J., Goncalves, L., Mareev, V., Riecansky, I., Kenda, M. F., Alonso, A., Lopez-Sendon, J. L., Rosengren, A., Buser, P., Okay, T., Sychov, O., Fox, K., Wood, D., Crijns, H., Mcgregor, K., Mulder, B., Priori, S., Ryden, L., Tavazzi, L., Vahanian, A., Vardas, P., Sarkisyan, K., Glogar, H. D., Frick, M., Pachinger, O., Zwick, R., Vrints, C., Van Hertbruggen, E., Vercammen, M., Sysmans, T., Schroeder, E., Domange, J., De Pril, H., De Vriese, J., Van Hecke, T., Legrand, V., Gillon, M. -F., Richardy, M., Doneux, P., Petrov, I., Jorgova, J., Starcevic, B., Eeckhout, E., Berger, A., Prudent, V., Camenzind, E., Masson, N., Zambartas, C., Kleanthous, H., Stellova, B., Aschermann, M., Simek, S., Kautzner, J., Karmazin, V., Svab, P., Indrak, J., Branny, M., Hladilova, K., Kala, P., Cappelen, H., Jensen, L. O., Gitt, A., Gehrke, K., am Rhein, L., Erbel, R., Gutersohn, A., Eggebrecht, H., Al Khani, M., Rosenberger, A., Vogelsberg, H., Klepzig, H., Schmidt, A., Silber, S., Mau, B., Leuner, C., Czyborra, K., Reuschling, C., Muno, E., Nauheim, B., Kleber, F., Rux, S., Saad, A., Elabady, M., Beiras, A. C., Fernandez, J. S., del Arno, F. N., Romo, A. I., Fernandez, J. M. C., Mayoreal, A. R., Rebanal, F. J. R., de la Borbolla, M. G., Chaparro, M., Brotons, C., Miralda, C. P., Vila i Perez, S. I., Aviles, F. F., de la Fuente Galan, L., Vinuela, P. T., de Torres, F. M., Mora, J., Rodriguez, I. S., Bustamante, I. P., Fernandez, P. L. S., Torrent, J. L. D., Gil, J. L. D., Perpinan, J., Motilla, V. P., Juango, M. S. A., Berjon-Reyero, J., Moreno, R. M., Guerrero, J. C. F., Savolainen, K., Syvanne, M., Cohen-Solal, A., Oboa, A. -S., Bassand, J. P., Espinosa, D. P., Jouet, V., Cedex, B., Montalescot, G., Gallois, V., Daubert, J. C., Clerc, J. M., Machecourt, J., Cottin, Y., Walker, D., Holland, F., Prosser, J., Muir, L., Barber, K., Cleland, J. G. F., Cook, J., Chapichadze, Z., Christos, I. S. A., Tsiavou, N., Chrysohoou, C., Manginas, A., Terrovitis, J., Kanakakis, J., Vavuranakis, M., Drakos, S., Farmakis, T., Samara, C., Papakosta, C., Bourantas, C., Michalis, L. K., Christos, M., Foussas, S., Adamopoulou, E., Marketou, M., Alotti, N., Basa, A. M., Vigh, A., Preda, I., Csoti, E., Keltai, M., Kerkovits, G., Hendler, A., Blatt, A., Yakov, B., Beyar, R., Shefer, A., Halon, D., Bentzvi, M., Avramovitch, N., Bakst, A., Saba, K., Cafri, C., Grosbard, A., Sheva, B., Margolis, B., Suleiman, K., Banai, S., Meerkin, D., Mosseri, M., Guita, P., Jabara, R., Jafari, J., Shitrit, D. B., Ghasan, D., Salameh, D., Brezins, M., van den Akker-Berman, L., Guetta, V., Hashomer, T., Rozenman, Y., Biagini, A., Berti, S., Ferrero, M., Colombo, A., Roccaforte, R., Milici, C., Scarpino, L., Salvi, A., Desideri, A., Sabbadin, D., Veneto, C., Galassi, A., Giuffrida, G., Rognoni, A., Vassanelli, C., Paffoni, P., Cioppa, A., Rubino, P., de Carlo, M., Petronio, A. S., Naccarella, F., Saia, F., Marzocchi, A., Maranga, S. S., Presbitero, P., Valsecchi, F., Esposito, G., Santini, N. M., Tubaro, M., Erglis, A., Narbute, I., Kavoliuniene, A., Zaliunas, R., Navickas, R., Luckute, D., Subkovas, E., Wagner, D., Vermeer, F., Lousberg, A., Fransen, H., Breeman, A., Tebbe, H., De Boer, M. J., van der Wal, M., Leenders, C. M., Veerhoek, M. J., Jansen, C., Bijl, M., Koppelaar, C., den Linden, V., Brons, R., Widdershofen, J. W. M. G., Broers, H., Kontny, F., Jonzon, M., Wodniecki, J., Tomasik, A., Trusz-Gluza, M., Nowak, S., Ruzyllo, W., Deptuch, T., Marques, J., Matias, F., Madeira, H., Oliveira, J., Sargento, L., Ionac, A., Dragulescu, I. S., Mut-Vitcu, B., Maximov, D., Dorobantu, M., Apetrei, E., Niculescu, R., Petrescu, V., Bucsa, A., Deleanu, D., Bucharest, Benedek, I. S., Hintea, T., Aronov, D., Tikhomirova, E., Kranjec, I., Prokselj, K., Kanic, V., Sepetoglu, A., Aytekin, S., Aytekin, V., Catakoglu, A. B., Parlar, H., Tufekcioglu, S., Ozyedek, Z., Baltali, M., Kiziltan, Vukovic, M., and Neskovic, A. N.

Subjects
Male, medicine.medical_specialty, Randomization, medicine.medical_treatment, Euro Heart Survey, Coronary Artery Disease, Revascularization, law.invention, Coronary artery disease, Randomized controlled trial, law, Internal medicine, Angioplasty, medicine, Humans, cardiovascular diseases, Angioplasty, Balloon, Coronary, Coronary Artery Bypass, CABG, Aged, Randomized Controlled Trials as Topic, business.industry, Coronary Artery Bypa, Patient Selection, PCI, Health Survey, Middle Aged, medicine.disease, Health Surveys, Surgery, Clinical trial, Stenosis, surgical procedures, operative, Clinical Trials, Phase III as Topic, Conventional PCI, Female, Cardiology and Cardiovascular Medicine, business, Human
Abstract

Aims: Revascularization in patients with coronary artery disease changed over the last two decades, favouring the number of patients treated by means of percutaneous coronary interventions (PCI) when compared with coronary artery bypass grafting (CABG). Many randomized controlled trials (RCTs) have been performed to compare these two competing revascularization techniques. Because of the strict enrolment criteria of RCTs in which highly selected patients are recruited, the applicability of the results may be limited in clinical practice. The current study evaluates to what extent patients in clinical practice were similar to those who participated in RCTs comparing PCI with CABG. Methods and results: Clinical characteristics and 1-year outcome of 4713 patients enrolled in the Euro Heart Survey on Coronary Revascularization were compared with 8647 patients who participated in 14 major RCTs, comparing PCI with CABG. In addition, we analysed which proportion of survey patients would have disqualified for trial participation (n = 3033, 64%), aiming at identifying differences between trial-eligible and trial-ineligible survey patients. In general, important differences were observed between trial participants and survey patients. Patients in clinical practice were older, more often had comorbid conditions, single-vessel disease, and left main stem stenosis when compared with trial participants. Almost identical differences were observed between trial-eligible and trial-ineligible survey patients. In clinical practice, PCI was the treatment of choice, even in patients who were trial-ineligible (46% PCI, 26% CABG, 28% medical). PCI remained the preferred treatment option in patients with multi-vessel disease (57% in trial-eligible and 40% in trial-ineligible patients, respectively, P < 0.001); yet, the risk profile of patients treated by PCI was better than that for patients treated either by CABG or by medical therapy. In the RCTs, there was no mortality difference between PCI and CABG. In clinical practice, however, we observed 1-year unadjusted survival benefit for PCI vs. CABG (2.9 vs. 5.4%, P < 0.001). Survival benefit was only observed in trial-ineligible patients (3.3 vs. 6.2%, P < 0.001). Conclusion: Many patients in clinical practice were not represented in RCTs. Moreover, only 36% of these patients were considered eligible for participating in a trial comparing PCI with CABG. We demonstrated that RCTs included younger patients with a better cardiovascular risk profile when compared with patients in everyday clinical practice. This study highlights the disparity between patients in clinical practice and patients in whom the studies that provide the evidence for treatment guidelines are performed. © The European Society of Cardiology 2006. All rights reserved.

Published
2006

10. Whole body biodistribution and radiation dosimetry in humans of a new PET ligand, [(18)F]-FEPPA, to image translocator protein (18 kDa)

Author

Romina Mizrahi, Sylvain Houle, Irina Vitcu, Pablo Rusjan, Alvina Ng, Peter M. Bloomfield, and Alan A. Wilson

Subjects
Adult, Male, Cancer Research, Biodistribution, Pyridines, Whole body imaging, Ligands, Receptors, GABA, Translocator protein, medicine, Dosimetry, Humans, Radiology, Nuclear Medicine and imaging, Anilides, Tissue Distribution, Whole Body Imaging, Radiometry, biology, medicine.diagnostic_test, business.industry, Chemistry, Oncology, Internal dose, Positron emission tomography, Organ Specificity, Positron-Emission Tomography, Pet ligand, biology.protein, Female, Whole body, Nuclear medicine, business
Abstract

[(18)F]-FEPPA is a translocator protein (18 kDa, TSPO) positron emission tomography (PET) radiotracer. Radiation dosimetry was estimated from the whole body biodistribution, taking into consideration TSPO rs6971 (Ala147Thr) polymorphism.[(18)F]-FEPPA whole body PET scans were acquired for six healthy subjects. Time-activity curves were generated from regions of interest of nine organs, from which normalized accumulated activities were calculated and thus internal dose, using OLINDA/EXM 1.1. Genotyping of rs6971, associated with high- and low-affinity [(18)F]-FEPPA binding (high-affinity binder (HAB) and low-affinity binder (LAB)), was performed.Five subjects exhibited the C/C (HAB) allele, and the other carried the minor allele T/T (LAB). The LAB whole body biodistribution showed highest radioactivity accumulation in bladder, whereas in HABs, the spleen received the highest dose. The effective dose of the single LAB (16.3 μSv/MBq) was 23 % less than the mean of the HABs (21.0 ± 2.9 μSv/MBq). When including all subjects, the effective dose was 20.2 ± 3.0 μSv/MBq.[(18)F]-FEPPA radiation dose is consistent with other (18)F-labeled radioligands and the Ala147Thr genotype agreed with [(18)F]-FEPPA distribution.

Published
2012

11. Biodistribution and radiation dosimetry of the serotonin 5-HT₆ ligand [¹¹C]GSK215083 determined from human whole-body PET

Author

Robert A, Comley, Cristian, Salinas, Romina, Mizrahi, Irina, Vitcu, Alvina, Ng, William, Hallett, Nicholas, Keat, Alan A, Wilson, Eugenii A, Rabiner, Marc, Laruelle, and Sylvain, Houle

Subjects
Adult, Male, Time Factors, Adolescent, Dose-Response Relationship, Radiation, Ligands, Young Adult, Organ Specificity, Positron-Emission Tomography, Receptors, Serotonin, Injections, Intravenous, Quinolines, Humans, Female, Tissue Distribution, Whole Body Imaging, Carbon Radioisotopes, Sulfones, Radiometry
Abstract

We measured the whole-body distribution of IV-injected [¹¹C]GSK215083, a new 5-HT₆ antagonist PET tracer, as a function of time in adult subjects, in order to determine the radiation exposure.After injection with a single bolus of [¹¹C]GSK215083 (range 330-367 MBq; mean 346 MBq), PET emission data were acquired for approximately 120 min in six subjects (three males and three females). Five organs were identified as exhibiting uptake above background. For these, regions of interest were delineated on emission images, and time-activity curves (TAC) generated. Residence times were calculated as the area under the curve of the TAC, normalized to injected activities and standard values of organ volumes. Dosimetry calculations were then performed using the computer program OLINDA/EXM 1.0.The mean effective dose averaged over both males and females (deviation) was estimated to be 7.7 ± 1.0 μSv/MBq (male 7.0 ± 0.4; female 8.5 ± 0.6). For the effective dose equivalent, the corresponding values are 7.8 ± 1.2 μSv/MBq (male 6.8 ± 0.5; female 8.9 ± 0.1). The organ receiving the highest dose was the lung, with an average equivalent dose of 25.6 ± 6.9 μSv/MBq (male 20.8 ± 5.6; female 30.4 ± 4.4).The estimated radiation dose for [¹¹C]GSK215083 is consistent with those for other neuroreceptor ligands labeled with carbon-11. The somewhat higher dose estimate for females compared to males may reflect the difference in observed residence times and representative differences in the male and female phantoms used for dosimetry calculations. Based on conventionally accepted dose limits, [¹¹C]GSK215083 may be used for multiple PET scans in the same subject.

Published
2011

12. Side effects profile in humans of (11)C-(+)-PHNO, a dopamine D(2/3) agonist ligand for PET

Author

Sylvain Houle, Alvina Ng, Alan A. Wilson, Irina Vitcu, and Romina Mizrahi

Subjects
Agonist, medicine.diagnostic_test, Chemistry, medicine.drug_class, Stereochemistry, Ligand, Receptors, Dopamine D2, Receptors, Dopamine D3, Ligands, Positron emission tomography, Dopamine receptor D2, Positron-Emission Tomography, Pet ligand, Oxazines, medicine, Humans, Regression Analysis, Radiology, Nuclear Medicine and imaging, Selectivity, Receptor
Abstract

TO THE EDITOR: 11C-(+)-4-propyl-9-hydroxynaphthoxazine ((+)-PHNO) is a new PET ligand developed by our group. Binding assays show that (+)-PHNO displays high affinity and selectivity for the D2 receptor ( [1][1] ). Recently, it has been noted that 11C-(+)-PHNO has a preferential affinity and

Published
2010

13. Unusual Cause of Heart Failure in a 65-Year-Old Woman

Author

Mirela Cleopatra Tomescu, Mioara Cocora, Adelina Mavrea, Dan Rusinaru, Ioana Citu, Bogdan Mut-Vitcu, and Stefan Iosif Dragulescu M.D.

Subjects
medicine.medical_specialty, Angina, Pseudoaneurysm, Internal medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, cardiovascular diseases, Myocardial infarction, Heart Aneurysm, Aged, Ultrasonography, Heart Failure, Mitral regurgitation, business.industry, Cardiac Rupture, Mitral Valve Insufficiency, medicine.disease, Surgery, Cardiac surgery, Heart failure, Infective endocarditis, cardiovascular system, Cardiology, Female, Tomography, X-Ray Computed, Cardiology and Cardiovascular Medicine, business
Abstract

Left ventricular (LV) free wall rupture is a potentially lethal mechanical complication after myocardial infarction (MI). Pericardial adhesions or slow extracardiac leak and pericardial inflammation may result in a contained cardiac rupture. LV pseudoaneurysm is a relatively uncommon clinical entity. It may occur after MI, but also as a complication of infective endocarditis, cardiac surgery, or trauma. Patients developing LV pseudoaneurysm after MI may present angina pectoris or signs of congestive heart failure (HF) but often are asymptomatic. Surgery is the treatment of choice for LV pseudoaneurysms diagnosed in the first months after MI. The management of chronic LV pseudoaneurysms is still subject of debate. This report highlights a 65-year-old patient newly hospitalized for acute decompensated HF who was diagnosed with a large chronic LV pseudoaneurysm and severe mitral regurgitation. The patient underwent successful resection of the pseudoaneurysm and patch repair of the ruptured ventricular wall.

Published
2008

14. Quetiapine extended-release versus immediate-release formulation: a positron emission tomography study

Author

Hiroyuki Uchida, Irina Vitcu, Penny Barsoum, Shitij Kapur, Alain Gendron, Jeffrey M. Goldstein, and David C. Mamo

Subjects
Adult, Male, Dibenzothiazepines, Adolescent, medicine.drug_class, Atypical antipsychotic, Pharmacology, Trough (economics), Hypnotic, Quetiapine Fumarate, Pharmacokinetics, medicine, Humans, Dosing, Cross-Over Studies, Receptors, Dopamine D2, Middle Aged, Crossover study, Corpus Striatum, Diagnostic and Statistical Manual of Mental Disorders, Psychiatry and Mental health, Pharmacodynamics, Delayed-Action Preparations, Positron-Emission Tomography, Schizophrenia, Female, Antipsychotic Agents
Abstract

OBJECTIVE: The pharmacokinetic and pharmacodynamic profile of the immediate-release (IR) formulation of quetiapine is characterized by a rapid peak in plasma level and striatal dopamine D(2) receptor occupancy, followed by a rapid decrease to baseline levels, necessitating the use of twice-daily dosing. An extended-release (XR) formulation of quetiapine is currently being developed to achieve similar efficacy using a once-daily dosing regimen. We compared the central D(2) receptor binding between the IR and XR formulations. METHOD: In this open-label, crossover positron emission tomography study using [(11)C]-raclopride, we compared the central D(2) receptor binding potential at expected peak and trough plasma levels using equivalent daily doses of the IR and XR formulations (300, 600, and 800 mg/day) in 12 subjects. Data were collected from April 2002 to May 2003. RESULTS: The mean plasma level of quetiapine at trough was significantly lower than that at peak for all dose groups of both formulations except for IR 300 and 800 mg (all p values < .05), while the mean plasma level did not differ significantly between formulations at trough and peak. The mean occupancy at peak was significantly higher than that at trough for all dose groups other than IR 800 mg/day (all p values < .05) and did not differ significantly between formulations at trough and peak. CONCLUSION: Once-daily dosing of the XR formulation gives peak and trough plasma levels and central D(2) receptor occupancy comparable to twice-daily dosing of the IR formulation. These data should be considered while determining equivalent doses, as well as switching strategies.

Published
2008

15. First human evidence of d-amphetamine induced displacement of a D2/3 agonist radioligand: A [11C]-(+)-PHNO positron emission tomography study

Author

Ariel Graff, Matthäus Willeit, Nathalie Ginovart, Alan A. Wilson, Irina Vitcu, Pablo Rusjan, Philip Seeman, Sylvain Houle, and Shitij Kapur

Subjects
Agonist, Adult, Male, medicine.medical_specialty, Dextroamphetamine, medicine.drug_class, Globus Pallidus, chemistry.chemical_compound, ddc:616.89, Dopamine, Internal medicine, Oxazines, medicine, Radioligand, Humans, Amphetamine, Neurotransmitter, Corpus Striatum/diagnostic imaging/metabolism, Putamen/diagnostic imaging/metabolism, Globus Pallidus/diagnostic imaging/metabolism, Pharmacology, Dopamine Agonists/chemical synthesis, Chemistry, Dextroamphetamine/pharmacology, Putamen, Brain, Corpus Striatum, Oxazines/chemical synthesis, Psychiatry and Mental health, Endocrinology, Globus pallidus, Positron-Emission Tomography, Dopamine Agonists, Catecholamine, Caudate Nucleus/diagnostic imaging/metabolism, Female, Caudate Nucleus, Brain/diagnostic imaging/metabolism, medicine.drug
Abstract

Imaging the competition between D(2/3) radioligands and endogenous dopamine is so far the only way to measure dopamine release in the living human brain. The dopamine D(2) receptor exists in a high (D(2)(high)) and a low-affinity state for dopamine. Under physiological conditions, dopamine is expected to bind to D(2)(high) only. [(11)C]-(+)-4-propyl-9-hydroxynaphthoxazine ((+)-PHNO) is the first D(2/3) agonist radioligand for positron emission tomography (PET) imaging in humans. Since [(11)C]-(+)-PHNO is expected to bind preferentially to D(2)(high), it should be particularly vulnerable to competition with endogenous dopamine. Nine healthy subjects participated in two PET scans, one after administration of d-amphetamine and one after placebo. [(11)C]-(+)-PHNO PET test re-test variability was determined in 11 healthy subjects. Binding potentials (BPs) were calculated for caudate, putamen, ventral striatum, and globus pallidus. d-Amphetamine led to a significant decrease of [(11)C]-(+)-PHNO BPs in caudate (-13.2%), putamen (-20.8%), and ventral striatum (-24.9%), but not in globus pallidus (-6.5%). d-Amphetamine-induced displacement correlated with serum d-amphetamine levels in all regions but caudate. This is the first report on competition between endogenous dopamine and a D(2/3) agonist radioligand in humans. [(11)C]-(+)-PHNO PET might be a superior measure for release of endogenous dopamine than PET employing conventional D(2/3) antagonist radioligands.

Published
2007

16. Striatal vs extrastriatal dopamine D2 receptors in antipsychotic response - a double-blind PET study in schizophrenia

Author

Robert B. Zipursky, Nathalie Ginovart, David C. Mamo, Irina Vitcu, Alan A. Wilson, Shitij Kapur, and Ofer Agid

Subjects
Male, Dyskinesia, Drug-Induced, Pyrrolidines, medicine.medical_treatment, Dopamine, Salicylamides, Haloperidol, Receptor, Serotonin, 5-HT2C, Prospective Studies, Antipsychotic drugs, Psychomotor Agitation, Raclopride, Middle Aged, Risperidone, Magnetic Resonance Imaging, Psychiatry and Mental health, Schizophrenia, Dopamine receptor, Olanzapine, Female, Schizophrenic Psychology, Psychology, Antipsychotic Agents, medicine.drug, Cognition -- Data processing, Adult, medicine.medical_specialty, Psychosis, Serotonin, Adolescent, Muscarinic Antagonists, Double-Blind Method, Dopamine receptor D2, Internal medicine, medicine, Humans, Antipsychotic, Benztropine, Psychiatric Status Rating Scales, Pharmacology, Receptors, Dopamine D2, Dopamine antagonist, medicine.disease, Prolactin, Neostriatum, Endocrinology, Positron-Emission Tomography, Dopamine Antagonists, Neuroscience
Abstract

Blockade of dopamine D2 receptors remains a common feature of all antipsychotics. It has been hypothesized that the extrastriatal (cortical, thalamic) dopamine D2 receptors may be more critical to antipsychotic response than the striatal dopamine D2 receptors. This is the first double-blind controlled study to examine the relationship between striatal and extrastriatal D2 occupancy and clinical effects. Fourteen patients with recent onset psychosis were assigned to low or high doses of risperidone (1 mg vs 4 mg/day) or olanzapine (2.5 mg vs 15 mg/day) in order to achieve a broad range of D2 occupancy levels across subjects. Clinical response, side effects, striatal ([11C]-raclopride-positron emission tomography (PET)), and extrastriatal ([11C]-FLB 457-PET) D2 receptors were evaluated after treatment. The measured D2 occupancies ranged from 50 to 92% in striatal and 4 to 95% in the different extrastriatal (frontal, temporal, thalamic) regions. Striatal and extrastriatal occupancies were correlated with dose, drug plasma levels, and with each other. Striatal D2 occupancy predicted response in positive psychotic symptoms (r=0.62, p=0.01), but not for negative symptoms (r=0.2, p=0.5). Extrastriatal D2 occupancy did not predict response in positive or negative symptoms. The two subjects who experienced motor side effects had the highest striatal occupancies in the cohort. Striatal D2 blockade predicted antipsychotic response better than frontal, temporal, and thalamic occupancy. These results, when combined with the preclinical data implicating the mesolimbic striatum in antipsychotic response, suggest that dopamine D2 blockade within specific regions of the striatum may be most critical for ameliorating psychosis in schizophrenia., peer-reviewed

Published
2007

17. Temporal difference modeling of the blood-oxygen level dependent response during aversive conditioning in humans: effects of dopaminergic modulation

Author

Ariel Graff-Guerrero, Shitij Kapur, Adrian P. Crawley, Mahesh Menon, Mark A. Smith, Jimmy Jensen, and Irina Vitcu

Subjects
Adult, Male, Time Factors, Adolescent, Dopamine, Conditioning, Classical, behavioral disciplines and activities, Dopamine Uptake Inhibitors, Neural Pathways, medicine, Image Processing, Computer-Assisted, Humans, Amphetamine, Biological Psychiatry, Blood-oxygen-level dependent, Putamen, Ventral striatum, Ventral Tegmental Area, Classical conditioning, Galvanic Skin Response, Middle Aged, Magnetic Resonance Imaging, Electric Stimulation, Ventral tegmental area, Oxygen, Substantia Nigra, medicine.anatomical_structure, Globus pallidus, nervous system, Dopamine Antagonists, Haloperidol, Female, Psychology, Neuroscience, Reinforcement, Psychology, psychological phenomena and processes, medicine.drug
Abstract

Background The prediction error (PE) hypothesized by the temporal difference model has been shown to correlate with the phasic activity of dopamine neurons during reward learning and the blood-oxygen level dependent (BOLD) response during reward and aversive conditioning tasks. We hypothesized that dopamine would modulate the PE related signal in aversive conditioning and that haloperidol would reduce PE related activity, while an acute dose of amphetamine would increase PE related activity in the ventral striatum. Methods Healthy participants took an acute dose of amphetamine, haloperidol, or placebo. We used functional magnetic resonance imaging (fMRI) to measure the BOLD signal while they carried out an aversive conditioning task, using cutaneous electrical stimulation as the unconditioned stimulus (US) and yellow and blue circles as conditioned stimulus (CS+ and CS−, respectively). Results Prediction error related BOLD activity was seen only in the ventral striatum in the placebo subjects. The subjects given amphetamine showed a wider network of PE related BOLD activity, including the ventral striatum, globus pallidus, putamen, insula, anterior cingulate, and substantia nigra/ventral tegmental area. Haloperidol subjects did not show PE related activity in any of these regions. Conclusions Our results provide the first demonstration that the modulation of dopamine transmission affects both the physiological correlates and PE related BOLD activity during aversive learning.

Published
2006

18. An automated method for the extraction of regional data from PET images

Author

Irina Vitcu, Douglas Hussey, Suhara Tetsuya, Sylvain Houle, David C. Mamo, Pablo Rusjan, Nathalie Ginovart, Fumihiko Yasuno, and Shitij Kapur

Subjects
Computer science, Neuroscience (miscellaneous), Models, Biological, Software, Region of interest, medicine, Brain positron emission tomography, Humans, Radiology, Nuclear Medicine and imaging, Segmentation, Image analysis, Temporal cortex, Reproducibility, Electronic Data Processing, medicine.diagnostic_test, business.industry, Brain, Reproducibility of Results, Pattern recognition, Magnetic Resonance Imaging, Psychiatry and Mental health, Positron emission tomography, Positron-Emission Tomography, Artificial intelligence, business, Nuclear medicine
Abstract

Manual drawing of regions of interest (ROIs) on brain positron emission tomography (PET) images is labour intensive and subject to intra- and inter-individual variations. To standardize analysis and improve the reproducibility of PET measures, we have developed image analysis software for automated quantification of PET data. The method is based on the individualization of a set of standard ROIs using a magnetic resonance (MR) image co-registered with the PET image. To evaluate the performance of this automated method, the software-based quantification has been compared with conventional manual quantification of PET images obtained using three different PET radiotracers: [ 11 C]-WAY 100635, [ 11 C]-raclopride and [ 11 C]-DASB. Our results show that binding potential estimates obtained using the automated method correlate highly with those obtained by trained raters using manual delineation of ROIs for frontal and temporal cortex, thalamus, and striatum (global intraclass correlation coefficient > 0.8). For the three radioligands, the software yields time–activity data that are similar (within 8%) to those obtained by manual quantification, eliminates investigator-dependent variability, considerably shortens the time required for analysis and thus provides an alternative method for accurate quantification of PET data.

Published
2005

19. Inflammatory response after dexamethasone eluting coronary stent implantation

Author

B, Mut-Vitcu, S I, Drăgulescu, Andreea, Drăgulescu, A, El Kahlout, Adriana, Coroban, Daniela, Maximov, and M, Slovenski

Subjects
Inflammation, Male, Anti-Inflammatory Agents, Coronary Disease, Middle Aged, Dexamethasone, C-Reactive Protein, Drug Delivery Systems, Treatment Outcome, Risk Factors, Humans, Female, Stents, Prospective Studies
Abstract

C-reactive protein (CRP) elevation after coronary stent implantation is a predictor for recurrence. We prospectively evaluated the inflammatory response after dexamethasone eluting stent implantation in a native coronary artery by serial measurement of plasma level C-reactive protein.We investigated patients undergoing primary successful implantation of a single dexamethasone stent (Dexamet, Abbott Vascular Devices, Redwood City, CA, USA) in a native coronary artery. We analyzed plasma concentrations of CRP by immunoturbidimetric assay before stent implantation and 12, 24, 48 and 72 hours after the procedure. Patients on anti-inflammatory drugs or with evidences of inflammatory conditions were excluded.Seventeen patients (mean age 62+/-9 years, 12 males) were enrolled. The presentation was unstable angina in 13 patients and stable angina in 4 patients. Eighteen stents were implanted as follows: 16 type B lesions (88%), 1 type C lesions (6%) and 1 type A lesion (6%), located in LM in 2 patients (11%), LAD in 8 (44%), LCX/OM in 7 (39%), and RCA in 1 patient (6%). The mean CRP increased from 5.6+/-2.2 mg/l at baseline to a maximum of 6.7+/-2.1 mg/l and than decreased to 5.0+/-1.2 mg/l at 72 hours. At 72 hours plasma concentration of CRP was lower than baseline in 11 patients (65%) and higher in 6 (35%).Inflammatory response to dexamethasone stent implantation in a native coronary artery is low and peaks at 24 hours. At 72 hours after stent implantation, mean CRP decreased comparing with baseline, CRP becoming lower in 65% patients. Using the stent itself as a platform for drug delivery may be an opportunity to modulate the inflammatory response to coronary stent implantation.

Published
2004

20. Oligodontia Is Caused by Mutation in LTBP3, the Gene Encoding Latent TGF-β Binding Protein 3

Author

Benjamin A. Alman, Irina Vitcu, Abdul Noor, John B. Vincent, Christian Windpassinger, Mahwish Khalid, Muhammad Rafiq, Mahmood Nasir Malik, Marija Orlic, and Muhammad Ayub

Subjects
Male, Heterozygote, Candidate gene, Nonsense mutation, Oligodontia, Biology, Consanguinity, 03 medical and health sciences, 0302 clinical medicine, Bone Density, Report, Genetics, Humans, Genetics(clinical), Pakistan, RNA, Messenger, Gene, Genetics (clinical), Anodontia, DNA Primers, Oligonucleotide Array Sequence Analysis, 030304 developmental biology, 0303 health sciences, Bone Development, Base Sequence, Chromosomes, Human, Pair 11, Binding protein, Homozygote, Heterozygote advantage, 030206 dentistry, Disease gene identification, Molecular biology, Body Height, Pedigree, Latent TGF-beta binding protein, Phenotype, Latent TGF-beta Binding Proteins, Codon, Nonsense, Female
Abstract

We have identified a consanguineous Pakistani family where oligodontia is inherited along with short stature in an autosomal-recessive fashion. Increased bone density was present in the spine and at the base of the skull. Using high-density single-nucleotide polymorphism microarrays for homozygosity mapping, we identified a 28 Mb homozygous stretch shared between affected individuals on chromosome 11q13. Screening selected candidate genes within this region, we identified a homozygous nonsense mutation, Y774X, within LTBP3, the gene for the latent TGF-beta binding protein 3, an extracellular matrix protein believed to be required for osteoclast function.

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