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21. No increased prevalence of malignancies among first-degree relatives of 800 patients with chronic myeloid leukemia : a population-based study in Sweden

Author

Gunnarsson, N., Höglund, Martin, Stenke, L., Sandin, F., Bjorkholm, M., Dreimane, A., Lambe, M., Markevarn, B., Olsson-Stromberg, Ulla, Wadenvik, H., Richter, J., Sjalander, A., Gunnarsson, N., Höglund, Martin, Stenke, L., Sandin, F., Bjorkholm, M., Dreimane, A., Lambe, M., Markevarn, B., Olsson-Stromberg, Ulla, Wadenvik, H., Richter, J., and Sjalander, A.

Published
2017
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22. No increased prevalence of malignancies among first-degree relatives of 800 patients with chronic myeloid leukemia: a population-based study in Sweden

Author

Gunnarsson, N, primary, Höglund, M, additional, Stenke, L, additional, Sandin, F, additional, Björkholm, M, additional, Dreimane, A, additional, Lambe, M, additional, Markevärn, B, additional, Olsson-Strömberg, U, additional, Wadenvik, H, additional, Richter, J, additional, and Själander, A, additional

Published
2017
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23. Increased prevalence of prior malignancies and autoimmune diseases in patients diagnosed with chronic myeloid leukemia

Author

Gunnarsson, Niklas, Höglund, M., Stenke, L., Wållberg-Jonsson, Solveig, Sandin, F., Björkholm, M., Dreimane, A., Lambe, M., Markevärn, Berit, Olsson-Strömberg, U., Wadenvik, H., Richter, J., Själander, Anders, Gunnarsson, Niklas, Höglund, M., Stenke, L., Wållberg-Jonsson, Solveig, Sandin, F., Björkholm, M., Dreimane, A., Lambe, M., Markevärn, Berit, Olsson-Strömberg, U., Wadenvik, H., Richter, J., and Själander, Anders

Abstract

We recently reported an increased incidence of second malignancies in chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKI). To elucidate whether this increase may be linked, not to TKI but rather to a hereditary or acquired susceptibility to develop cancer, we estimated the prevalence of malignancies, autoimmune disease (AD) and chronic inflammatory disease (CID) in CML patients prior to their CML diagnosis. Nationwide population-based registers were used to identify patients diagnosed with CML in Sweden 2002-2012 and to estimate the prevalence of other malignancies, AD and CID prior to their CML diagnosis. For each patient with CML, five matched controls were selected from the general population. Conditional logistic regression was used to calculate odds ratios (OR). Nine hundred and eighty-four CML patients were assessed, representing more than 45 000 person-years of follow-up. Compared with matched controls, the prevalence of prior malignancies and AD was elevated in CML patients: OR 1.47 (95% confidence interval (CI) 1.20-1.82) and 1.55 (95% CI 1.21-1.98), respectively. No associations were detected between CML and previous CID. An increased prevalence of other malignancies and AD prior to the diagnosis of CML suggest that a hereditary or acquired predisposition to cancer and/or autoimmunity is involved in the pathogenesis of CML.

Published
2016
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24. Efficacy and Safety of Low-Dose Aspirin in Polycythemia Vera

Author

Landolfi, R, Marchioli, R, Kutti, J, Gisslinger, H, Tognoni, G, Patrono, C, Barbui, T, Finazzi, G, Pusterla, S, Falanga, A, Galli, M, Wadenvik, H, Gastl, G, Ludescher, C, Lutz, D, Girschikofsky, M, Michlmayr, G, Rechberger, E, Niessner, H, Ivansich, E, Rain, Jd, Chommienne Thomas, C, Hehlmann, R, Engelich, G, Kohne, E, Kramer, A, Christakis, Ji, Papaioannou, M, Gerotziafas, G, O'Donnell, R, Bennett, M, Lugassy, G, Ellis, M, Eldor, A, Naparstek, E, Marilus, R, Leoni, P, Rupoli, S, Scortechini, Ar, Agostini, V, Volpe, E, Calmieri, F, Volpe, A, Storti, G, Ciampa, A, Dammacco, F, Lauta, Vm, Ranieri, G, Rizzi, R, Orsola, S, Tura, S, Finelli, C, Marino, G, Rossi, G, Almici, C, Capucci, A, Zanetti, F, Giustolisi, R, Cacciola, Rr, Cacciola, E, Peta, A, Magro, D, Frigerio, G, Alberio, F, Beretta, A, Bonferroni, M, Raviolo, A, Ferrini, Prl, Grossi, A, Fabbri, A, Nardelli, S, Centra, A, Musolino, C, Bellomo, G, Trincali, O, Spatari, Giovanna, Foa, P, Gerli, G, Carraro, Mc, Zanella, A, Lurlo, A, Barraco, F, Torelli, G, Marietta, M, Pogliani, E, Miccolis, Ir, La Rocca, A, Puglisi, A, Sardeo, G, Rotoli, B, Martinelli, V, Ciancia, R, Cardarelli, A, Cimino, R, Fasanaro, A, Randi, Ml, Rizzoli, V, Caramatti, C, Gaeta, L, Lazzarino, M, Passamonti, F, Lazzola, M, Malabarba, L, Natale, D, Pulini, S, Davi, G, Gugliotta, L, Ilariucci, F, De Candia, E, Eugenio, S, Amadori, S, Buccisano, F, Mandelli, F, Montefusco, E, Petti, Mc, Spadea, A, Carotenuto, M, Morelli, A, Nobile, M, Longinotti, M, Pardini, Sm, Lauria, F, Buccalossi, A, Gentili, S, Mazza, P, Cervellera, M, Maggi, A, Di Francesco, A, Pasqualoni, E, Chisesi, T, Polacco, A, Capnist, G, Rodeghiero, F, Ruggeri, M, Arrizabalaga, B, Remacha, A, De Mendiguren, Bp, Hernandez Nieto, L, Hernandez Garcia, Mt, Gonzalez Brito, G, Machado, P, Garcia, G, Villegas, A, Pena, A, Fernandez, Ag, Carbonell, F, Del Arco, A, Back, H, Stenke, L, Hansen, S, Larsson, G, Stromblad, G, Lauri, B, Ryden, Bo, Linder, O, Lundholm, Bg, Lannemyr, O, Strandberg, M, Andreasson, B, Stockelberg, D, Pasquariello, F, Tichelli, A, Otremba, B, Hinrichs, Hf, Weber Stadelmann, W, Bareford, D, Oscier, Dg, Bowey, N, Taylor, Pc, de Gaetano, G, Najean, Y, Pearson, Tc, Di Blasio, A, Atashkar, S, Mari, E, Tamayo, D, Borelli, G, Ferri, B, Marfisi, Rm, Olivieri, M, Polidoro, A, Spoltore, R, Levantesi, G, Di Mascio, R, Miceli, G, Sperti, G, Correale, E, Vermjlen, J, and Collins, R.

Subjects
Aspirin, medicine.medical_specialty, business.industry, food and beverages, General Medicine, medicine.disease, Thrombosis, Pulmonary embolism, Venous thrombosis, Polycythemia vera, Relative risk, Internal medicine, Anesthesia, Cardiology, Medicine, Myocardial infarction, business, Contraindication, medicine.drug
Abstract

background The use of aspirin for the prevention of thrombotic complications in polycythemia vera is controversial. methods We enrolled 518 patients with polycythemia vera, no clear indication for aspirin treatment, and no contraindication to such treatment in a double-blind, placebo-controlled, randomized trial to assess the safety and efficacy of prophylaxis with low-dose aspirin (100 mg daily). The two primary end points were the cumulative rate of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes and the cumulative rate of nonfatal myocardial infarction, nonfatal stroke, pulmonary embolism, major venous thrombosis, or death from cardiovascular causes. The mean duration of follow-up was about three years. results Treatment with aspirin, as compared with placebo, reduced the risk of the combined end point of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes (relative risk, 0.41; 95 percent confidence interval, 0.15 to 1.15; P=0.09) and the risk of the combined end point of nonfatal myocardial infarction, nonfatal stroke, pulmonary embolism, major venous thrombosis, or death from cardiovascular causes (relative risk, 0.40; 95 percent confidence interval, 0.18 to 0.91; P=0.03). Overall mortality and cardiovascular mortality were not reduced significantly. The incidence of major bleeding episodes was not significantly increased in the aspirin group (relative risk, 1.62; 95 percent confidence interval, 0.27 to 9.71). conclusions Low-dose aspirin can safely prevent thrombotic complications in patients with polycythemia vera who have no contraindications to such treatment.

Published
2004
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25. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia

Author

Saglio G, Kim DW, Issaragrisil S, le Coutre P, Etienne G, Lobo C, Pasquini R, Clark RE, Hochhaus A, Hughes TP, Gallagher N, Hoenekopp A, Dong M, Haque A, Larson RA, Kantarjian HM, Moiraghi B, Perez M, Greil R, Valent P, Bosly A, Martiat P, Noens L, André M, Verhoef G, Conchon M, Souza C, Nonino A, Hungria V, Zanichelli MA, Colturato V, Forrest D, Lipton JH, Savoie ML, Delage R, Lalancette M, Quintero G, Gomez M, Klamova H, Faber E, Bjerrum OW, Fredriksen H, Vestergaard H, Marcher C, Kamel H, Elzawam H, Porkka K, Remes K, Reiffers J, Guilhot F, Facon T, Tulliez M, Guerci Bresler AP, Nicolini FE, Charbonnier A, Rea D, Johnson Ansah A, Legros L, Harousseau JL, Rigal Huguet F, Escoffre M, Gardembas M, Guyotat D, Cahn JY, Gattermann N, Ottmann O, Niederwieser D, Stegelmann F, Schafhausen P, Brümmendorf T, Duyster J, Blumenstengel K, Scheid C, Kneba M, Kwong YL, Masszi T, Petrini M, Alimena G, Di Raimondo F, Rosti G, Rotoli B, Pungolino E, Amadori S, Abruzzese E, Fioritoni G, Lauria F, Bosi A, Martelli M, Rambaldi A, Ferrara F, Nobile F, Gobbi M, Carella AM, Orlandi EM, Leoni P, Tiribelli M, Levis A, Imamura M, Takahashi N, Tsukamoto N, Chiba S, Nagai T, Okamoto S, Miura O, Kurokawa M, Ohnishi K, Toba K, Nakao S, Tomita A, Miyamura K, Hino M, Maeda Y, Kimura A, Kawaguchi T, Miyazaki Y, Nakaseko C, Jinnai I, Matsuda A, Matsumura I, Ishikawa J, Ohyashiki K, Okada M, Usuki K, Kobayashi Y, Ohishi K, Imai K, Miyawaki S, Kanda Y, Park SY, Kim HJ, Sohn SK, Lee KH, Jung CW, Ong TC, Gómez Almaguer D, Kassack J, Ossenkoppele GJ, Gedde Dahl T, Hjorth Hansen H, Jedrzejczak W, Dmoszynska A, Starzak Dwozdz J, Holowiecki J, Kyrcz Krzemieñ S, Kuliczkowski K, Zaritsky A, Turkina A, Pospelova T, Goh YT, Koh LP, Demitrovicova L, Mistrik M, Ruff P, Louw V, Dreosti LM, Novitzky N, Cohen G, Cervantes F, Cañizo C, de Paz R, del Castillo S, Perez Encinas M, Sanz Alonso M, Marin F, Pérez López R, Hernandez Boluda J, Echeveste Gutierrez MA, Odriozola J, Herrera P, Steegman JL, Conde E, Lopez P, Giraldo P, Boque C, Heredia B, Font AJ, Rodriguez RF, Rodriguez MJ, Batlle J, Stenke L, Lehmann S, Wadenvik H, Simonsson B, Markevärn B, Själander A, Richter J, Bjoreman M, Eriksson KM, Chalandon Y, Shih LY, Yao M, Wang MC, Jootar S, Bunworasate U, Ulkü B, Haznedar R, Undar B, Sahin B, Marin D, Smith G, Byrne J, Holyoake T, Kalaycio M, Akard L, Heaney M, Al Janadi A, Goldberg S, Powell B, Harker WG, Shea T, Gingrich R, Glass J, Paquette R, Siegrist C, Woodson M, Fehrenbacher L, Koh H, Flinn I, Arrowsmith E, Ervin T, Guerra M, Wallach H, Berry W, Burke J, Edenfield W, Guzley G, Davis J, Richards D, Schlossman D, Kolibaba K, Alemany C, Savin M, Robbins G, Lopez J, Goldman JM, Camm J, Schiffer CA, Sargent D.J., PANE, FABRIZIO, Saglio, G, Kim, Dw, Issaragrisil, S, le Coutre, P, Etienne, G, Lobo, C, Pasquini, R, Clark, Re, Hochhaus, A, Hughes, Tp, Gallagher, N, Hoenekopp, A, Dong, M, Haque, A, Larson, Ra, Kantarjian, Hm, Moiraghi, B, Perez, M, Greil, R, Valent, P, Bosly, A, Martiat, P, Noens, L, André, M, Verhoef, G, Conchon, M, Souza, C, Nonino, A, Hungria, V, Zanichelli, Ma, Colturato, V, Forrest, D, Lipton, Jh, Savoie, Ml, Delage, R, Lalancette, M, Quintero, G, Gomez, M, Klamova, H, Faber, E, Bjerrum, Ow, Fredriksen, H, Vestergaard, H, Marcher, C, Kamel, H, Elzawam, H, Porkka, K, Remes, K, Reiffers, J, Guilhot, F, Facon, T, Tulliez, M, Guerci Bresler, Ap, Nicolini, Fe, Charbonnier, A, Rea, D, Johnson Ansah, A, Legros, L, Harousseau, Jl, Rigal Huguet, F, Escoffre, M, Gardembas, M, Guyotat, D, Cahn, Jy, Gattermann, N, Ottmann, O, Niederwieser, D, Stegelmann, F, Schafhausen, P, Brümmendorf, T, Duyster, J, Blumenstengel, K, Scheid, C, Kneba, M, Kwong, Yl, Masszi, T, Petrini, M, Alimena, G, Di Raimondo, F, Rosti, G, Rotoli, B, Pane, Fabrizio, Pungolino, E, Amadori, S, Abruzzese, E, Fioritoni, G, Lauria, F, Bosi, A, Martelli, M, Rambaldi, A, Ferrara, F, Nobile, F, Gobbi, M, Carella, Am, Orlandi, Em, Leoni, P, Tiribelli, M, Levis, A, Imamura, M, Takahashi, N, Tsukamoto, N, Chiba, S, Nagai, T, Okamoto, S, Miura, O, Kurokawa, M, Ohnishi, K, Toba, K, Nakao, S, Tomita, A, Miyamura, K, Hino, M, Maeda, Y, Kimura, A, Kawaguchi, T, Miyazaki, Y, Nakaseko, C, Jinnai, I, Matsuda, A, Matsumura, I, Ishikawa, J, Ohyashiki, K, Okada, M, Usuki, K, Kobayashi, Y, Ohishi, K, Imai, K, Miyawaki, S, Kanda, Y, Park, Sy, Kim, Hj, Sohn, Sk, Lee, Kh, Jung, Cw, Ong, Tc, Gómez Almaguer, D, Kassack, J, Ossenkoppele, Gj, Gedde Dahl, T, Hjorth Hansen, H, Jedrzejczak, W, Dmoszynska, A, Starzak Dwozdz, J, Holowiecki, J, Kyrcz Krzemieñ, S, Kuliczkowski, K, Zaritsky, A, Turkina, A, Pospelova, T, Goh, Yt, Koh, Lp, Demitrovicova, L, Mistrik, M, Ruff, P, Louw, V, Dreosti, Lm, Novitzky, N, Cohen, G, Cervantes, F, Cañizo, C, de Paz, R, del Castillo, S, Perez Encinas, M, Sanz Alonso, M, Marin, F, Pérez López, R, Hernandez Boluda, J, Echeveste Gutierrez, Ma, Odriozola, J, Herrera, P, Steegman, Jl, Conde, E, Lopez, P, Giraldo, P, Boque, C, Heredia, B, Font, Aj, Rodriguez, Rf, Rodriguez, Mj, Batlle, J, Stenke, L, Lehmann, S, Wadenvik, H, Simonsson, B, Markevärn, B, Själander, A, Richter, J, Bjoreman, M, Eriksson, Km, Chalandon, Y, Shih, Ly, Yao, M, Wang, Mc, Jootar, S, Bunworasate, U, Ulkü, B, Haznedar, R, Undar, B, Sahin, B, Marin, D, Smith, G, Byrne, J, Holyoake, T, Kalaycio, M, Akard, L, Heaney, M, Al Janadi, A, Goldberg, S, Powell, B, Harker, Wg, Shea, T, Gingrich, R, Glass, J, Paquette, R, Siegrist, C, Woodson, M, Fehrenbacher, L, Koh, H, Flinn, I, Arrowsmith, E, Ervin, T, Guerra, M, Wallach, H, Berry, W, Burke, J, Edenfield, W, Guzley, G, Davis, J, Richards, D, Schlossman, D, Kolibaba, K, Alemany, C, Savin, M, Robbins, G, Lopez, J, Goldman, Jm, Camm, J, Schiffer, Ca, and Sargent, D. J.

Published
2010

26. ECMO/PPHN

Author

Montgomery V. L., Eberly S. M., Mellgren K., Skogby M., Friberg L. G., Wadenvik H., Mellgren G., Maglajlić, S., Jovanović, I., Parezanović, V., Vušurović, V., Koš, R., Laban-Nestorović, S., Mustafa, Iqbal, Sjamsubin, Embing, Martona, Marteye, Samudra, Spemato Heru, Rachmat, Yusuf, Rahayoe, Anna Ulfah, and Samsu, Zuswahyudha

Published
1996
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27. PROGRESSION OF CHRONIC PHASE CHRONIC MYELOID LEUKEMIA TO ADVANCED PHASE ON TKI THERAPY : A POPULATION BASED ANALYSIS FROM THE SWEDISH CML REGISTER

Author

Söderlund, Stina, Dahlen, T., Creignou, M., Sandin, F., Olsson-Stromberg, Ulla, Dreimane, A., Markevaem, B., Sjaelander, A., Wadenvik, H., Stenke, L., Richter, J., Höglund, Martin, Söderlund, Stina, Dahlen, T., Creignou, M., Sandin, F., Olsson-Stromberg, Ulla, Dreimane, A., Markevaem, B., Sjaelander, A., Wadenvik, H., Stenke, L., Richter, J., and Höglund, Martin

Published
2015

28. Progression of chronic phase chronic myeloid leukemia to advanced phase on tki therapy : A population based analysis from the Swedish CML register

Author

Soderlund, S., Dahlen, T., Creignou, M., Sandin, F., Olsson-Stromberg, U., Dreimane, A., Markevaem, B., Själander, Anders, Wadenvik, H., Stenke, L., Richter, J., Hoeglund, M., Soderlund, S., Dahlen, T., Creignou, M., Sandin, F., Olsson-Stromberg, U., Dreimane, A., Markevaem, B., Själander, Anders, Wadenvik, H., Stenke, L., Richter, J., and Hoeglund, M.

Published
2015

30. REAL WORLD DATA ON CHRONIC MYELOID LEUKEMIA - A REPORT FROM THE SWEDISH POPULATION BASED CML-REGISTRY in HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, vol 95, issue , pp 337-338

Author

Höglund, M, Bjoreman, M, Björkholm, M, Brune, M, Ekblom, M, Hellström, K, Lehmann, S, Ljungman, P, Malm, Claes, Markevarn, B, Sandin, F, Stenke, L, Wadenvik, H, Wahlin, A, Richter, J, Simonsson, B, Höglund, M, Bjoreman, M, Björkholm, M, Brune, M, Ekblom, M, Hellström, K, Lehmann, S, Ljungman, P, Malm, Claes, Markevarn, B, Sandin, F, Stenke, L, Wadenvik, H, Wahlin, A, Richter, J, and Simonsson, B

Abstract

n/a

Published
2010

35. Prevention of deep-vein thrombosis and pulmonary embolism after total hip replacement. Comparison of low-molecular-weight heparin and unfractionated heparin

Author

Bengt Eriksson, Kälebo P, Ba, Anthymyr, Wadenvik H, Tengborn L, and Risberg B

Subjects
Male, Heparin, Blood Loss, Surgical, Phlebography, Chemical Fractionation, Middle Aged, Thrombophlebitis, Antibodies, Molecular Weight, Double-Blind Method, Risk Factors, Factor Xa, Humans, Female, Hip Prosthesis, Prospective Studies, Pulmonary Embolism, Radionuclide Imaging, Aged
Abstract

In a prospective, randomized, double-blind study, the efficacy and safety of a low-molecular-weight heparin were compared with those of unfractionated sodium heparin (standard heparin) in 136 patients who had elective total hip replacement. The patients received subcutaneous injection of either 5000 international units of low-molecular-weight heparin once daily or 5000 international units of standard heparin three times a day. Treatment with low-molecular-weight heparin began twelve hours before the operation, and treatment with standard heparin began two hours preoperatively; both regimens were continued for ten days. Twelve days postoperatively, bilateral ascending phlebography was performed in 122 patients, sixty-three in the treatment group that received low-molecular-weight heparin and fifty-nine in the treatment group that received standard heparin. Pulmonary scintigraphy was performed in 127 patients. Deep-vein thrombosis was diagnosed in forty-four patients: nineteen (30 per cent) of the sixty-three who received low-molecular-weight heparin and twenty-five (42 per cent) of the fifty-nine who received standard heparin. All but four patients, two from each treatment group, were asymptomatic. The difference in the total rate of thrombosis in the two groups was not significant (p = 0.189). However, thrombosis occurred in the thigh in only six (10 per cent) of the patients who received low-molecular-weight heparin but in eighteen (31 per cent) of those who received standard heparin, a significant difference (p = 0.011). Pulmonary embolism was detected in twenty-seven patients: eight (12.3 per cent) of those who received low-molecular-weight heparin and nineteen (30.6 per cent) of those who received standard heparin. Only three patients had clinical signs of embolism. Pulmonary embolism was significantly more frequent in the group that received standard heparin (p = 0.016). Total loss of blood and the total amount of blood that was transfused were significantly reduced in the patients who received low-molecular-weight heparin compared with those who received standard heparin. Prophylaxis was not discontinued because of hemorrhage in any patient. The efficacy of low-molecular-weight heparin was superior to that of standard heparin in the prevention of femoral thrombosis and pulmonary embolism, although the over-all incidence of deep-vein thrombosis was not statistically different.(ABSTRACT TRUNCATED AT 400 WORDS)

Published
1991

43. Good adherence to imatinib therapy among patients with chronic myeloid leukemia--a single-center observational study.

Author

Jönsson S, Olsson B, Söderberg J, Wadenvik H, Jönsson, Sofia, Olsson, Bob, Söderberg, Jenny, and Wadenvik, Hans

Abstract

Previous studies have suggested that adherence to imatinib therapy can be an obstacle among patients with chronic myeloid leukemia (CML). We studied adherence to imatinib therapy among CML patients treated at the Sahlgrenska University Hospital. We identified all CML patients that were alive at the 1st of January 2010 (n = 70). Nineteen patients were excluded due to a history of allogenic hematopoietic stem cell transplantation, and nine were excluded due to treatment with other tyrosine kinase inhibitors. Thirty-eight out of 42 patients (90%) treated with imatinib accepted inclusion in the study. The patients were interviewed in a structured way, and adherence was evaluated in a standardized way using the nine-item Morisky Medication Adherence Scale that ranges from 1 to 13. A Morisky score ≤10 indicates nonadherence and ≥11 indicates adherence. In addition, predefined follow-up questions were asked to identify factors known to influence adherence to therapy. In contrast to previous studies, our patients showed good adherence to imatinib therapy with a mean Morisky score of 12.3 out of 13 (range, 9-13). The interviews revealed factors known to predict adherence to therapy, namely being well informed and having frequent contact with a single hematologist. Furthermore, the patients had easy access to the treating clinic and felt that they took part in decisions concerning their disease and treatment. We show that adherence to imatinib can be very good in CML patients, and we suggest that simple measures such as increased patient information and continuity of care will increase adherence in patients with CML. [ABSTRACT FROM AUTHOR]

Published
2012
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47. A transforming growth factor-beta1-mediated bystander immune suppression could be associated with remission of chronic idiopathic thrombocytopenic purpura.

Author

Andersson, P O, Stockelberg, D, Jacobsson, S, and Wadenvik, H

Abstract

Bystander immune suppression has been demonstrated in experimental models of oral immune tolerance induction. This phenomenon is associated with expression of transforming growth factor (TGF)-beta1 and T-helper cell (Th) 2 cytokines. We have studied serum levels of Th cytokines and B- and T-lymphocyte subsets in chronic idiopathic thrombocytopenic purpura (ITP), a disorder in which the production of platelet autoantibodies might be caused by a cytokine network dysregulation. Forty-six patients with ITP were separated into three groups depending on the platelet count (pltc): (1) < 50 x 10(9)/l, (2) 50-150 x 10(9)/l and (3) > 150 x 10(9)/l. We found significantly elevated plasma levels of the Th3 cytokine TGF-beta1 in patients with pltc >150x10(9)/l (23.5+/-2.8ng/ml), compared with patients with pltc <50x10(9)/l (2.3+/-0.6 ng/ml; P<0.0001), patients with pltc 50-150x 10(9)/l (7.2+/-1.7 ng/ml; P<0.0001) and healthy volunteers (9.8+/-1.3 ng/ml; P<0.01). The serum levels of the Thl cytokines interleukin (IL)-2 and interferon (IFN)-y were below the detection limits of the assays. Likewise, the Th2 cytokine IL-4 was not detectable or was very low both in patients and controls. The serum levels of IL-10, a Th2 cytokine, were within the assay range and patients with pltc <50 x 10(9)/l had significantly lower levels (0.6+/-0.1 pg/ml) than both patients with pltc 50-150 x 10(9)/l (1.8 +/- 0.1 pg/ml; P<0.005) and healthy volunteers (1.4+/-0.1 pg/ml; P<0.005). Furthermore, patients with pltc <50 x 10(9)/l and splenectomised patients had significantly higher levels of CD4 + CD25 + activated T cells [26.2 +/- 14.8% (P<0.05) and 26.7+/-11.9% (P<0.005), respectively] than healthy controls (16.5+/-4.0%). Also, the number of natural killer (NK) cells among patients with pltc >150 x 10(9)/l were significantly elevated (26.6+/-16.0%; P<0.05) compared with controls (17.4+/-7.6%). In conclusion, our data corroborate previous findings of elevated numbers of activated T cells in chronic ITP patients with active disease, but neither a clear-cut Th1 nor a Th2 serum cytokine profile could be established. However, ITP in remission was associated with elevated TGF-beta1, which might be a part of a bystander immune suppression. We propose that the effect of possible expression of TGF-beta1 by oral immune tolerance induction deserves to be explored in ITP patients with an active disease. [ABSTRACT FROM AUTHOR]

Published
2000
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48. Inhaled prostacyclin and platelet function after cardiac surgery and cardiopulmonary bypass.

Author

Haraldsson, A, Kieler-Jensen, N, Wadenvik, H, and Ricksten, S E

Abstract

Objective: To study the effects of 6 h inhalation of aerosolized prostacyclin (PGI2) on platelet function.Design: In a prospective, double-blind, randomized study, 28 patients scheduled for elective cardiac surgery requiring cardiopulmonary bypass (CPB), received either 0.9% sodium chloride (n = 8), PGI2 5 microg x ml(-1) (n = 10) or PGI2 10 microg x ml(-1) (n = 10) as an aerosol for 6 h postoperatively.Setting: Cardiothoracic intensive care unit at a university hospital.Interventions: All patients were studied immediately after surgery during mechanical ventilation and sedation. The PGI2 solutions or saline were administered with a jet nebulizer.Measurements and Results: Bleeding time and chest tube drainage were measured. Blood samples for platelet aggregation, thrombelastography (TEG) and analysis of coagulation parameters and the stable prostacyclin metabolite 6-keto-PGF1alpha were obtained immediately before inhalation and after 2, 4 and 6 h of inhalation. After 6 h of PGI2 inhalation, regardless of administered dose, there was a lower rate of platelet aggregation and a lower maximal increase in light transmission in response to adenosine diphosphate (ADP) than in the control group. The TEG variable reaction time (R) was prolonged after 4 and 6 h of inhalation in the PGI2 group receiving 10 microg x ml(-1). There were no differences between groups with respect to bleeding time and chest tube drainage or any of the other variables examined.Conclusion: Inhalation of PGI2 for 6 h in patients after cardiac surgery is associated with impaired platelet aggregation detected by in vitro techniques, with no in vivo signs of platelet dysfunction. [ABSTRACT FROM AUTHOR]

Published
2000

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