43 results on '"Pree I"'
Search Results
2. An Easy-to-Use Prognostic Model for Survival Estimation for Patients with Symptomatic Long Bone Metastases
- Author
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Willeumier, J.J., van der Linden, Y.M., van der Wal, C.W.P.G., Jutte, P.C., van der Velden, J.M., Smolle, M.A., van der Zwaal, P., Koper, P., Bakri, L., de Pree, I., Leithner, A., Fiocco, M., and Dijkstra, P.D.S.
- Published
- 2018
- Full Text
- View/download PDF
3. Robust scheduling for a One Stop Shop palliative radiotherapy clinic using genetic algorithms
- Author
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Hoffmans-Holtzer, N., Smolenaers, L., Peeters, R., Swart, N., Tims, O., De Pree, I., Slagter, C., Olofsen-van Acht, M., Hoogeman, M., Balvert, M., Petit, S., Tilburg University, Econometrics and Operations Research, and Research Group: Operations Research
- Published
- 2022
4. SP-0210 Innovations in patient care through RTT advanced practice
- Author
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Otto-Vollaard, L., primary, Quint, S., additional, Nuyttens, J., additional, Steinvoort-Draat, I., additional, de Pree, I., additional, and Tims, O., additional
- Published
- 2022
- Full Text
- View/download PDF
5. Murine Mobilized Peripheral Blood Stem Cells Have a Lower Capacity than Bone Marrow to Induce Mixed Chimerism and Tolerance
- Author
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Koporc, Z., Pilat, N., Nierlich, P., Blaha, P., Bigenzahn, S., Pree, I., Selzer, E., Sykes, M., Muehlbacher, F., and Wekerle, T.
- Published
- 2008
- Full Text
- View/download PDF
6. Dexamethasone for the Prevention of a Pain Flare After Palliative Radiation Therapy for Painful Bone Metastases: The Multicenter Double-Blind Placebo-Controlled 3-Armed Randomized Dutch DEXA Study
- Author
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Linden, Y.M. van der, Westhoff, P.G., Stellato, R.K., Baardwijk, A., Vries, K. de, Ong, F., Wiggenraad, R., Bakri, B., Wester, G., Pree, I. De, Veelen, L. van, Budiharto, T., Schippers, M., Reyners, A.K., Graeff, A. de, Linden, Y.M. van der, Westhoff, P.G., Stellato, R.K., Baardwijk, A., Vries, K. de, Ong, F., Wiggenraad, R., Bakri, B., Wester, G., Pree, I. De, Veelen, L. van, Budiharto, T., Schippers, M., Reyners, A.K., and Graeff, A. de
- Abstract
Contains fulltext : 225317.pdf (Publisher’s version ) (Open Access), PURPOSE: After radiation therapy for painful bone metastases, up to 44% of patients report a pain flare (PF). Our study compared 2 dose schedules of dexamethasone versus placebo to prevent PF. METHODS AND MATERIALS: This double-blind, randomized, placebo-controlled trial allocated patients with painful bone metastases from solid tumors randomly to receive 8 mg dexamethasone before radiation therapy followed by 3 daily doses (group A), 8 mg dexamethasone followed by 3 doses of placebo (group B), or 4 doses of placebo (group C). Patients reported worst pain scores, study medication side effects, and opioid intake before treatment and thereafter daily for 14 days and on day 28. PF was defined as at least a 2-point increase on a 0 to 10 pain scale with no decrease in opioid intake or a 25% or greater increase in opioid intake with no decrease in pain score, followed by a return to baseline or lower. The primary analysis was by intention to treat with patients who had missing data classified as having a PF. RESULTS: From January 2012 to April 2016, 295 patients were randomized. PF incidence was 38% for group A, 27% for group B, and 39% for group C (P = .07). Although patients in group B had the lowest PF incidence, a relatively high percentage did not return to baseline pain levels, indicating pain progression. The mean duration of PF was 2.1 days for group A, 4.5 days for group B, and 3.3 days for group C (P = .0567). Dexamethasone postponed PF occurrence; in group A 52% occurred on days 2 to 5 versus 73% in group B and 99% in group C (P = .02). Patients in group A reported lower mean pain scores on days 2 to 5 than those in group B or C (P < .001). Side effects were similar. CONCLUSIONS: There was insufficient evidence that dexamethasone reduced the incidence of radiation-induced PF. However, dexamethasone postponed the occurrence of PF and led to lower mean pain scores on days 2 to 5.
- Published
- 2020
7. PO-1251: Whole brain radiotherapy: to treat or not to treat?
- Author
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Otto-Vollaard, L., primary, Quint, S., additional, De Pree, I., additional, Steinvoort, I., additional, Tims, O., additional, and Nuyttens, J.J., additional
- Published
- 2020
- Full Text
- View/download PDF
8. The majority of allergen-specific IgE in the blood of allergic patients does not originate from blood-derived B cells or plasma cells
- Author
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Eckl-Dorna, J., Pree, I., Reisinger, J., Marth, K., Chen, K.-W., Vrtala, S., Spitzauer, S., Valenta, R., and Niederberger, V.
- Published
- 2012
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- View/download PDF
9. Inhibition of CD23-dependent facilitated allergen binding to B cells following vaccination with genetically modified hypoallergenic Bet v 1 molecules
- Author
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Pree, I., Shamji, M. H., Kimber, I., Valenta, R., Durham, S. R., and Niederberger, V.
- Published
- 2010
- Full Text
- View/download PDF
10. Cigarette smoke facilitates allergen penetration across respiratory epithelium
- Author
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Gangl, K., Reininger, R., Bernhard, D., Campana, R., Pree, I., Reisinger, J., Kneidinger, M., Kundi, M., Dolznig, H., Thurnher, D., Valent, P., Chen, K.-W., Vrtala, S., Spitzauer, S., Valenta, R., and Niederberger, V.
- Published
- 2009
- Full Text
- View/download PDF
11. Effectiveness and toxicity of conventional radiotherapy treatment for painful spinal metastases: a detailed course of side effects after opposing fields versus a single posterior field technique
- Author
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Westhoff, P.G., Graeff, A. de, Monninkhof, E.M., Pree, I. de, Vulpen, M. van, Leer, J.W.H., Marijnen, C.A.M., Linden, Y.M. van der, and Dutch Bone Metastasis Study Grp
- Subjects
Spinal metastases ,Toxicity ,Bone metastases ,Palliative radiotherapy ,Side effects - Published
- 2018
12. Pain flare, complexity and analgesia in bone oligometastases treated with stereotactic body radiation therapy
- Author
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Loi, M. (Mauro), Klass, N.D. (Natalie D.), De Vries, K.C. (Kim C.), Fleury, E. (Emmanuelle), Van Zwienen, M. (Marieke), Pree, I. (Ilse) de, Nuyttens, J.J.M.E. (Joost), Loi, M. (Mauro), Klass, N.D. (Natalie D.), De Vries, K.C. (Kim C.), Fleury, E. (Emmanuelle), Van Zwienen, M. (Marieke), Pree, I. (Ilse) de, and Nuyttens, J.J.M.E. (Joost)
- Abstract
The aim of our study was to assess the incidence of pain flare and the effectiveness of stereotactic body radiotherapy (SBRT) in pain management of patients with bone oligometastases. We evaluated 48 patients accounting for 54 treatments. The Edmonton Classification System for Cancer Pain (ECS-CP) was applied to identify indicators of treatment-resistant pain, in patients with active pain (NRS ≥ 2) at baseline. Statistical analysis was performed to identify predictors of pain flare and pain control. Pain flare occurred in 38% of treated patients (n = 18/48): No correlation was found between pain flare and patient- or treatment-related variables. In the subset of patients with active pain at baseline (n = 23), pain control was obtained in 62% of patients at 1 year; median time to pain progression after SBRT was 29 months (CI95% 6–52 months). Presence of ≥2ECS-CP features was correlated with earlier pain progression (4 vs. 30 months, p = 0.012). Pain flare occurred in 38% of cases irrespectively of steroid premedication and dose regimen. In patient with baseline active pain, durable pain control was obtained. Presence of ≥2 complexity indicators at the ECS-CP assessment was correlated with impaired pain control and may deserve future investigation in prospective studies.
- Published
- 2018
- Full Text
- View/download PDF
13. EP-1656: Influence factors on limited overall survival in palliative patients with lung cancer
- Author
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Klass, N., primary, De Pree, I., additional, Oomen-de Hoop, E., additional, Loi, M., additional, Otto-Vollaard, L., additional, Swaak-Kragten, A., additional, Van Zwienen, C., additional, and Nuyttens, J., additional
- Published
- 2018
- Full Text
- View/download PDF
14. Effectiveness and toxicity of conventional radiotherapy treatment for painful spinal metastases: a detailed course of side effects after opposing fields versus a single posterior field technique
- Author
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Westhoff, P.G., Graeff, A. de, Monninkhof, E.M., Pree, I. De, Vulpen, M. van, Leer, J.W.H., Marijnen, C.A., Linden, Y.M. van der, Westhoff, P.G., Graeff, A. de, Monninkhof, E.M., Pree, I. De, Vulpen, M. van, Leer, J.W.H., Marijnen, C.A., and Linden, Y.M. van der
- Abstract
Contains fulltext : 181900.pdf (Publisher’s version ) (Open Access)
- Published
- 2017
15. The role of natural killer T cells in costimulation blockade-based mixed chimerism
- Author
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Nierlich, P.N., Klaus, C., Bigenzahn, S., Pilat, N., Koporc, Zvonimir, Pree, I., Baranyi, U., Taniguchi, M., Muehlbacher, F., and Wekerle, T.
- Subjects
mixed chimerism ,transplantation ,tolerance ,NKT cells ,hemic and immune systems ,chemical and pharmacologic phenomena - Abstract
Distinct lymphocyte populations have been identified that either promote or impede the establishment of chimerism and tolerance through allogeneic bone marrow transplantation (BMT). Natural killer T (NKT) cells have pleiotropic regulatory properties capable of either augmenting or downmodulating various immune responses. We investigated in this study whether NKT cells affect outcome in mixed chimerism models employing fully mismatched nonmyeloablative BMT with costimulation blockade (CB). The absence of NKT cells had no detectable effect on chimerism or skin graft tolerance after conditioning with 3Gy total body irradiation (TBI), and a limited positive effect with 1Gy TBI. Stimulation of NKT cells with alpha-galactosylceramide (alpha-gal) at the time of BMT prevented chimerism and tolerance. Activation of recipient (as opposed to donor) NKT cells was necessary and sufficient for the alpha-gal effect. The detrimental effect of NKT activation was also observed in the absence of T cells after conditioning with in vivo T-cell depletion (TCD). NKT cells triggered rejection of BM via NK cells as chimerism and tolerance were not abrogated when NKT cells were stimulated in the absence of both NK cells and T cells. Thus, activation of NKT cells at the time of BMT overcomes the effects of CB, inhibiting the establishment of chimerism and tolerance.
- Published
- 2010
16. Cardiac metastases
- Author
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Al-Mamgani, A. (Abrahim), Baartman, L. (Lizette), Baaijens, M. (Margreet), Pree, I. (Ilse) de, Incrocci, L. (Luca), Levendag, P.C. (Peter), Al-Mamgani, A. (Abrahim), Baartman, L. (Lizette), Baaijens, M. (Margreet), Pree, I. (Ilse) de, Incrocci, L. (Luca), and Levendag, P.C. (Peter)
- Abstract
We report a case of esophageal cancer with symptomatic metastases to the heart; the patient was treated with short-course radiotherapy with good symptomatic relief. We reviewed the current literature regarding the epidemiology, clinical presentation, diagnostic tools, treatment modalities, and the prognosis of cardiac metastases. In this report we summarize the most recent autopsy studies (published between 1975 and 2007), in which we found an autopsy incidence of cardiac metastases of 2.3% among the general population, while the incidence among autopsies of cancer patients was 7.1%. Therefore, we share the opinion with others that there has been an increase in the incidence of cardiac metastases among cancer patients diagnosed after 1970, in comparison with the reported incidences in older series before 1970 (7.1% vs 3.8%; Kruskal-Wallis rank test; P = 0.039). Special attention was given to the role of radiotherapy in the management of cardiac metastases.
- Published
- 2008
- Full Text
- View/download PDF
17. SP-0296: Clinical implementation of Plan-of-the-Day strategies for cervical cancer
- Author
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Quint, S., primary, Hoogeman, M., additional, Ahmad, R., additional, Dhawtal, G., additional, Bondar, L., additional, de Pree, I., additional, Mens, J.W., additional, and Heijmen, B., additional
- Published
- 2013
- Full Text
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18. An On-line Adaptive Strategy for Cervical Cancer Patients Based on Pre-treatment Acquired Variable Bladder Filling CT-scans and In-room Bladder Volume Measurements
- Author
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Heijmen, B., primary, Bondar, L., additional, Mens, J., additional, Dhawtal, G., additional, Quint, S., additional, Ahmad, R., additional, de Pree, I., additional, and Hoogeman, M.S., additional
- Published
- 2010
- Full Text
- View/download PDF
19. IGRT IN EBRT FOR CERVICAL CANCER, A PLAN OF THE DAY STRATEGY
- Author
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Quint, S., primary, Hoogeman, M., additional, Ahmad, R., additional, Dhawtal, G., additional, Bondar, L., additional, de Pree, I., additional, Mens, J.W., additional, and Heijmen, B., additional
- Published
- 2009
- Full Text
- View/download PDF
20. TU-D-BRC-06: Towards Online Image Guided Radiotherapy for Cervical Cancer: Accurate Cervix-Uterus Prediction Based On Measured Bladder Volumes
- Author
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Bondar, M, primary, Hoogeman, M, additional, Dhawtal, G, additional, Mens, J, additional, Osorio, E Vasquez, additional, de Pree, I, additional, Quint, S, additional, Ahmad, R, additional, and Heijmen, B, additional
- Published
- 2009
- Full Text
- View/download PDF
21. PO-1040 Robust scheduling for a One Stop Shop palliative radiotherapy clinic using genetic algorithms.
- Author
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Hoffmans-Holtzer, N., Smolenaers, L., Peeters, R., Swart, N., Tims, O., De Pree, I., Slagter, C., Olofsen - van Acht, M., Hoogeman, M., Balvert, M., and Petit, S.
- Subjects
- *
GENETIC algorithms , *RADIOTHERAPY , *SCHEDULING - Published
- 2022
- Full Text
- View/download PDF
22. Palliative radiotherapy: New prognostic factors for patients with bone metastasis.
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Steinvoort-Draat IN, Otto-Vollaard L, Quint S, Tims JL, de Pree IMN, and Nuyttens JJ
- Subjects
- Humans, Male, Female, Prognosis, Aged, Middle Aged, Prospective Studies, Aged, 80 and over, Adult, Lung Neoplasms radiotherapy, Lung Neoplasms mortality, Lung Neoplasms pathology, Prostatic Neoplasms radiotherapy, Prostatic Neoplasms pathology, Prostatic Neoplasms mortality, Morphine therapeutic use, Breast Neoplasms pathology, Breast Neoplasms radiotherapy, Breast Neoplasms mortality, Kaplan-Meier Estimate, Sex Factors, Analgesics, Opioid therapeutic use, Bone Neoplasms secondary, Bone Neoplasms radiotherapy, Bone Neoplasms mortality, Palliative Care, Karnofsky Performance Status
- Abstract
Purpose: Many cancer patients develop bone metastases, however the prognosis of overall survival differs. To provide an optimal treatment for these patients, especially towards the end of life, a reliable prediction of survival is needed. The goal of this study was to find new clinical factors in relation to overall survival., Materials and Methods: Prospectively 22 clinical factors were collected from 734 patients. The Kaplan-Meier and Cox regression models were used., Results: Most patients were diagnosed with lung cancer (29%), followed by prostate (19.8%) and breast cancer (14.7%). Median overall survival was 6.4months. Fourteen clinical factors showed significance in the univariate analyses. In the multivariate analyses 6 factors were found to be significant for the overall survival: Karnofsky performance status, primary tumor, gender, total organs affected, morphine use and systemic treatment options after radiotherapy., Conclusion: Morphine use and systemic treatment options after radiotherapy, Karnofsky performance status, primary tumor, gender and total organs affected are strong prediction factors on overall survival after palliative radiotherapy in patients with bone metastasis. These factors are easily applicable in the clinic., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
23. Evaluating AI-generated CBCT-based synthetic CT images for target delineation in palliative treatments of pelvic bone metastasis at conventional C-arm linacs.
- Author
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Hoffmans-Holtzer N, Magallon-Baro A, de Pree I, Slagter C, Xu J, Thill D, Olofsen-van Acht M, Hoogeman M, and Petit S
- Subjects
- Humans, Female, Palliative Care, Pelvis, Tomography, X-Ray Computed, Cone-Beam Computed Tomography methods, Radiotherapy Planning, Computer-Assisted methods, Radiotherapy Dosage, Spiral Cone-Beam Computed Tomography, Pelvic Bones
- Abstract
Purpose: One-table treatments with treatment imaging, preparation and delivery occurring at one treatment couch, could increase patients' comfort and throughput for palliative treatments. On regular C-arm linacs, however, cone-beam CT (CBCT) imaging quality is currently insufficient. Therefore, our goal was to assess the suitability of AI-generated CBCT based synthetic CT (sCT) images for target delineation and treatment planning for palliative radiotherapy., Materials and Methods: CBCTs and planning CT-scans of 22 female patients with pelvic bone metastasis were included. For each CBCT, a corresponding sCT image was generated by a deep learning model in ADMIRE 3.38.0. Radiation oncologists delineated 23 target volumes (TV) on the sCTs (TVsCT) and scored their delineation confidence. The delineations were transferred to planning CTs and manually adjusted if needed to yield gold standard target volumes (TVclin). TVsCT were geometrically compared to TVclin using Dice coefficient (DC) and Hausdorff Distance (HD). The dosimetric impact of TVsCT inaccuracies was evaluated for VMAT plans with different PTV margins., Results: Radiation oncologists scored the sCT quality as sufficient for 13/23 TVsCT (median: DC = 0.9, HD = 11 mm) and insufficient for 10/23 TVsCT (median: DC = 0.7, HD = 34 mm). For the sufficient category, remaining inaccuracies could be compensated by +1 to +4 mm additional margin to achieve coverage of V95% > 95% and V95% > 98%, respectively in 12/13 TVsCT., Conclusion: The evaluated sCT quality allowed for accurate delineation for most targets. sCTs with insufficient quality could be identified accurately upfront. A moderate PTV margin expansion could address remaining delineation inaccuracies. Therefore, these findings support further exploration of CBCT based one-table treatments on C-arm linacs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
24. Dexamethasone for the Prevention of a Pain Flare After Palliative Radiation Therapy for Painful Bone Metastases: The Multicenter Double-Blind Placebo-Controlled 3-Armed Randomized Dutch DEXA Study.
- Author
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van der Linden YM, Westhoff PG, Stellato RK, van Baardwijk A, de Vries K, Ong F, Wiggenraad R, Bakri B, Wester G, de Pree I, van Veelen L, Budiharto T, Schippers M, Reyners AKL, and de Graeff A
- Subjects
- Adult, Aged, Aged, 80 and over, Analgesics, Opioid administration & dosage, Anti-Inflammatory Agents, Non-Steroidal administration & dosage, Bone Neoplasms secondary, Cancer Pain drug therapy, Cancer Pain epidemiology, Disease Progression, Double-Blind Method, Female, Humans, Intention to Treat Analysis, Male, Middle Aged, Netherlands, Outcome Assessment, Health Care, Pain Measurement, Palliative Care methods, Placebos administration & dosage, Time Factors, Bone Neoplasms radiotherapy, Cancer Pain prevention & control, Dexamethasone administration & dosage, Glucocorticoids administration & dosage, Symptom Flare Up
- Abstract
Purpose: After radiation therapy for painful bone metastases, up to 44% of patients report a pain flare (PF). Our study compared 2 dose schedules of dexamethasone versus placebo to prevent PF., Methods and Materials: This double-blind, randomized, placebo-controlled trial allocated patients with painful bone metastases from solid tumors randomly to receive 8 mg dexamethasone before radiation therapy followed by 3 daily doses (group A), 8 mg dexamethasone followed by 3 doses of placebo (group B), or 4 doses of placebo (group C). Patients reported worst pain scores, study medication side effects, and opioid intake before treatment and thereafter daily for 14 days and on day 28. PF was defined as at least a 2-point increase on a 0 to 10 pain scale with no decrease in opioid intake or a 25% or greater increase in opioid intake with no decrease in pain score, followed by a return to baseline or lower. The primary analysis was by intention to treat with patients who had missing data classified as having a PF., Results: From January 2012 to April 2016, 295 patients were randomized. PF incidence was 38% for group A, 27% for group B, and 39% for group C (P = .07). Although patients in group B had the lowest PF incidence, a relatively high percentage did not return to baseline pain levels, indicating pain progression. The mean duration of PF was 2.1 days for group A, 4.5 days for group B, and 3.3 days for group C (P = .0567). Dexamethasone postponed PF occurrence; in group A 52% occurred on days 2 to 5 versus 73% in group B and 99% in group C (P = .02). Patients in group A reported lower mean pain scores on days 2 to 5 than those in group B or C (P < .001). Side effects were similar., Conclusions: There was insufficient evidence that dexamethasone reduced the incidence of radiation-induced PF. However, dexamethasone postponed the occurrence of PF and led to lower mean pain scores on days 2 to 5., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
25. Pain flare, complexity and analgesia in bone oligometastases treated with stereotactic body radiation therapy.
- Author
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Loi M, Klass ND, De Vries KC, Fleury E, Van Zwienen M, de Pree I, and Nuyttens J
- Subjects
- Aged, Bone Neoplasms complications, Bone Neoplasms secondary, Cancer Pain epidemiology, Cancer Pain etiology, Dexamethasone therapeutic use, Disease Progression, Female, Glucocorticoids therapeutic use, Humans, Incidence, Male, Middle Aged, Pain Management, Pain Measurement, Palliative Care, Premedication, Retrospective Studies, Symptom Flare Up, Treatment Outcome, Analgesics, Non-Narcotic therapeutic use, Analgesics, Opioid therapeutic use, Bone Neoplasms radiotherapy, Cancer Pain therapy, Radiosurgery methods
- Abstract
The aim of our study was to assess the incidence of pain flare and the effectiveness of stereotactic body radiotherapy (SBRT) in pain management of patients with bone oligometastases. We evaluated 48 patients accounting for 54 treatments. The Edmonton Classification System for Cancer Pain (ECS-CP) was applied to identify indicators of treatment-resistant pain, in patients with active pain (NRS ≥ 2) at baseline. Statistical analysis was performed to identify predictors of pain flare and pain control. Pain flare occurred in 38% of treated patients (n = 18/48): No correlation was found between pain flare and patient- or treatment-related variables. In the subset of patients with active pain at baseline (n = 23), pain control was obtained in 62% of patients at 1 year; median time to pain progression after SBRT was 29 months (CI95% 6-52 months). Presence of ≥2ECS-CP features was correlated with earlier pain progression (4 vs. 30 months, p = 0.012). Pain flare occurred in 38% of cases irrespectively of steroid premedication and dose regimen. In patient with baseline active pain, durable pain control was obtained. Presence of ≥2 complexity indicators at the ECS-CP assessment was correlated with impaired pain control and may deserve future investigation in prospective studies., (© 2018 John Wiley & Sons Ltd.)
- Published
- 2018
- Full Text
- View/download PDF
26. Effectiveness and toxicity of conventional radiotherapy treatment for painful spinal metastases: a detailed course of side effects after opposing fields versus a single posterior field technique.
- Author
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Westhoff PG, de Graeff A, Monninkhof EM, de Pree I, van Vulpen M, Leer JWH, Marijnen CAM, and van der Linden YM
- Abstract
Background: Conventional radiotherapy for painful spinal metastases can be delivered with a single posterior-anterior (PA) or two opposed anterior-posterior (APPA) fields. We studied the effectiveness and toxicity of both techniques and studied whether treatment technique was predictive for abdominal and skin toxicity., Patients and Methods: Within the Dutch Bone Metastasis Study, 343 patients received 8 Gray in a single fraction or 24 Gray in six fractions for painful spinal metastases. Treatment technique was not randomized. At baseline and weekly during follow-up, patients reported pain and other physical complaints. Any complaint increasing within 4 weeks after treatment was noted as a side effect. Pain response was calculated according to international standards, taking into account changes in pain score and medication. Repeated measurement analyses and multivariate logistic analyses were performed., Results: Patients were mainly treated on the thoracic (34%) and lumbar (53%) spine and 73% received a PA field. Pain response was similar between both techniques (74%). In patients treated at the thoraco-lumbar and lumbar spine, with multiple fractions, significantly more abdominal complaints were noticed. In multivariate analysis, radiotherapy technique did not predict for side effects., Conclusion: Conventional radiotherapy of painful spinal metastases provides limited toxicity. Radiotherapy technique is not an independent predictor of abdominal and skin toxicity of irradiation., Competing Interests: Compliance with ethical standardsNo funding was received for this study.The authors declare that they have no conflict of interest.All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.Informed consent was obtained from all individual participants included in the study.
- Published
- 2018
- Full Text
- View/download PDF
27. Minor Antigen Disparities Impede Induction of Long Lasting Chimerism and Tolerance through Bone Marrow Transplantation with Costimulation Blockade.
- Author
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Bigenzahn S, Pree I, Klaus C, Pilat N, Mahr B, Schwaiger E, Nierlich P, Wrba F, and Wekerle T
- Subjects
- Animals, Female, Graft Survival immunology, Lymphocyte Depletion, Mice, Minor Histocompatibility Antigens immunology, Skin Transplantation, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets metabolism, Tissue Donors, Transplantation Conditioning, Transplantation, Homologous, Antigens immunology, Bone Marrow Transplantation, Immune Tolerance, Transplantation Chimera
- Abstract
Mixed chimerism and tolerance can be successfully induced in rodents through allogeneic bone marrow transplantation (BMT) with costimulation blockade (CB), but varying success rates have been reported with distinct models and protocols. We therefore investigated the impact of minor antigen disparities on the induction of mixed chimerism and tolerance. C57BL/6 (H2
b ) mice received nonmyeloablative total body irradiation (3 Gy), costimulation blockade (anti-CD40L mAb and CTLA4Ig), and 2 × 107 bone marrow cells (BMC) from either of three donor strains: Balb/c (H2d ) (MHC plus multiple minor histocompatibility antigen (mHAg) mismatched), B10.D2 (H2d ) or B10.A (H2a ) (both MHC mismatched, but mHAg matched). Macrochimerism was followed over time by flow cytometry and tolerance was tested by skin grafting. 20 of 21 recipients of B10.D2 BMC but only 13 of 18 of Balb/c BMC and 13 of 20 of B10.A BMC developed stable long-term multilineage chimerism ( p < 0.05 for each donor strain versus B10.D2). Significantly superior donor skin graft survival was observed in successfully established long-term chimeras after mHAg matched BMT compared to mHAg mismatched BMT ( p < 0.05). Both minor and major antigen disparities pose a substantial barrier for the induction of chimerism while the maintenance of tolerance after nonmyeloablative BMT and costimulation blockade is negatively influenced by minor antigen disparities. .- Published
- 2016
- Full Text
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28. A phase I study on the combination of neoadjuvant radiotherapy plus pazopanib in patients with locally advanced soft tissue sarcoma of the extremities.
- Author
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Haas RL, Gelderblom H, Sleijfer S, van Boven HH, Scholten A, Dewit L, Borst G, van der Hage J, Kerst JM, Nout RA, Hartgrink HH, de Pree I, Verhoef C, Steeghs N, and van Coevorden F
- Subjects
- Adult, Aged, Angiogenesis Inhibitors adverse effects, Extremities, Female, Humans, Indazoles, Male, Maximum Tolerated Dose, Middle Aged, Neoadjuvant Therapy methods, Pyrimidines adverse effects, Sulfonamides adverse effects, Young Adult, Angiogenesis Inhibitors administration & dosage, Chemoradiotherapy, Adjuvant methods, Pyrimidines administration & dosage, Sarcoma therapy, Soft Tissue Neoplasms therapy, Sulfonamides administration & dosage
- Abstract
Unlabelled: Accumulating evidence suggests significant synergism combining radiotherapy (RT) with angiogenesis targeted therapies. This multicenter prospective phase I clinical trial established the safety profile and recommended dose for further studies of pazopanib concurrent with preoperative RT in patients with extremity soft tissue sarcomas (ESTS) in curative setting., Methods: Patients with deep seated intermediate and high grade sarcomas, ≥ 5 cm, received once daily pazopanib (dose-escalation cohorts 400 mg, 600 mg and 800 mg) for 6 weeks and 50 Gy preoperative RT starting Day 8. Surgery was performed 5-7 weeks later. Toxicity was scored according to CTC criteria 4.0. Dose limiting toxicities (DLT) were divided into two separate sets; DLT-I being toxicities occurring during the 6-week chemoradiotherapy period within the radiation portals until day of surgery (designated as DLT-I) and those occurring perioperatively until Day 21 after surgery (DLT-II)., Results: A total of 12 patients were enrolled, 11 were evaluable (3 females and 8 males, median age 58 years, range 24-78 years, median tumor size 9 cm, range 5-15 cm). Ten underwent surgery. No increased toxicity inside the radiation fields was seen, but two of 10 patients (one each in the 400 mg and 600 mg cohorts) showed delayed wound healing after surgery. None of the patients showed significant volume reductions after RT. Evaluation of the resection specimen showed pathological (near) complete responses (≥ 95% necrosis rate) in four of 10 cases. Unexpectedly, grade 3 + hepatotoxicity led to premature pazopanib interruption in three of 11 (27%) of cases., Conclusion: Apart from hepatotoxicity, neoadjuvant pazopanib 800 mg daily in combination with 50 Gy seems tolerable; the regimen appears to demonstrate promising activity in ESTS and is the recommended dose for further studies.
- Published
- 2015
- Full Text
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29. Toward an individualized target motion management for IMRT of cervical cancer based on model-predicted cervix-uterus shape and position.
- Author
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Bondar L, Hoogeman M, Mens JW, Dhawtal G, de Pree I, Ahmad R, Quint S, and Heijmen B
- Subjects
- Adult, Aged, Artifacts, Female, Humans, Imaging, Three-Dimensional, Middle Aged, Movement, Neoplasm Staging, Predictive Value of Tests, Prone Position, Cervix Uteri diagnostic imaging, Radiotherapy Planning, Computer-Assisted methods, Radiotherapy, Intensity-Modulated methods, Tomography, X-Ray Computed, Uterine Cervical Neoplasms diagnostic imaging, Uterine Cervical Neoplasms radiotherapy
- Abstract
Background and Purpose: To design and evaluate a 3D patient-specific model to predict the cervix-uterus shape and position., Methods and Materials: For 13 patients lying in prone position, 10 variable bladder filling CT-scans were acquired, 5 at planning and 5 after 40Gy. The delineated cervix-uterus volumes in 2-5 pre-treatment CT-scans were used to generate patient-specific models that predict the cervix-uterus geometry by bladder volume. Model predictions were compared to delineations, excluding those used for model construction. The prediction error was quantified by the margin required around the predicted volumes to accommodate 95% of the delineated volume and by the predicted-to-delineated surface distance., Results: The prediction margin was significantly smaller (average 50%) than the margin encompassing the cervix-uterus motion. The prediction margin could be decreased (from 7 to 5mm at planning and from 10 to 8mm after 40Gy) by increasing (from 2 to 5) the number of CT-scans used for the model construction., Conclusion: For most patients, even with a model based on only two CT-scans, the prediction error was well below the margin encompassing the cervix-uterus motion. The described approach could be used to create prior to treatment, an individualized treatment strategy., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
30. Increasing treatment accuracy for cervical cancer patients using correlations between bladder-filling change and cervix-uterus displacements: proof of principle.
- Author
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Ahmad R, Hoogeman MS, Bondar M, Dhawtal V, Quint S, De Pree I, Mens JW, and Heijmen BJ
- Subjects
- Adult, Aged, Dose-Response Relationship, Radiation, Female, Humans, Middle Aged, Organ Size, Radiography, Radiotherapy Dosage, Uterine Cervical Neoplasms diagnostic imaging, Cervix Uteri diagnostic imaging, Urinary Bladder diagnostic imaging, Uterine Cervical Neoplasms radiotherapy
- Abstract
Purpose: To investigate application of pre-treatment established correlations between bladder-filling changes and cervix-uterus displacements in adaptive therapy., Materials and Methods: Thirteen cervical cancer patients participated in this prospective study. Pre-treatment, and after delivery of 40 Gy, a full bladder CT-scan was acquired, followed by voiding the bladder and acquisition of 4 other 3D scans in a 1h period with a naturally filling bladder (variable bladder filling CT-scans, VBF-scans). For the pre-treatment VBF-scans, linear correlations between bladder volume change and displacements of the tip of the uterus (ToU) and the center of mass (CoM) of markers implanted in the fornices of the vagina relative to the full bladder planning scan were established. Prediction accuracy of these correlation models was assessed by comparison with actual displacements in CT-scans, both pre-treatment and after 40 Gy. Inter-fraction ToU and marker-CoM displacements were derived from the established correlations and twice-weekly performed in-room bladder volume measurements, using a 3D ultrasound scanner., Results: Target displacement in VBF-scans ranged from up to 65 mm in a single direction to almost 0mm, depending on the patient. For pre-treatment VBF-scans, the linear correlation models predicted the mean 3D position change for the ToU of 26.1 mm±10.8 with a residual of only 2.2 mm±1.7. For the marker-CoM, the 8.4 mm±5.3 mean positioning error was predicted with a residual of 0.9 mm±0.7. After 40Gy, the mean ToU displacement was 26.8 mm±15.8, while prediction based on the pre-treatment correlation models yielded a mean residual error of 9.0 mm±3.7. Target positioning errors in the fractioned treatments were very large, especially for the ToU (-18.5mm±11.2 for systematic errors in SI-direction)., Conclusions: Pre-treatment acquired VBF-scans may be used to substantially enhance treatment precision of cervical cancer patients. Application in adaptive therapy is promising and warrants further investigation. For highly conformal (IMRT) treatments, the use of a full bladder drinking protocol results in unacceptably large systematic set-up errors., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2011
- Full Text
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31. The role of natural killer T cells in costimulation blockade-based mixed chimerism.
- Author
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Nierlich PN, Klaus C, Bigenzahn S, Pilat N, Koporc Z, Pree I, Baranyi U, Taniguchi M, Muehlbacher F, and Wekerle T
- Subjects
- Animals, Bone Marrow Transplantation, Chimerism, Female, Galactosylceramides pharmacology, Immune System, Immune Tolerance, Immunosuppressive Agents therapeutic use, Mice, Mice, Inbred BALB C, Mice, Inbred C3H, Mice, Inbred C57BL, Skin Transplantation methods, Whole-Body Irradiation, Killer Cells, Natural cytology, T-Lymphocytes cytology
- Abstract
Distinct lymphocyte populations have been identified that either promote or impede the establishment of chimerism and tolerance through allogeneic bone marrow transplantation (BMT). Natural killer T (NKT) cells have pleiotropic regulatory properties capable of either augmenting or downmodulating various immune responses. We investigated in this study whether NKT cells affect outcome in mixed chimerism models employing fully mismatched nonmyeloablative BMT with costimulation blockade (CB). The absence of NKT cells had no detectable effect on chimerism or skin graft tolerance after conditioning with 3Gy total body irradiation (TBI), and a limited positive effect with 1Gy TBI. Stimulation of NKT cells with alpha-galactosylceramide (alpha-gal) at the time of BMT prevented chimerism and tolerance. Activation of recipient (as opposed to donor) NKT cells was necessary and sufficient for the alpha-gal effect. The detrimental effect of NKT activation was also observed in the absence of T cells after conditioning with in vivo T-cell depletion (TCD). NKT cells triggered rejection of BM via NK cells as chimerism and tolerance were not abrogated when NKT cells were stimulated in the absence of both NK cells and T cells. Thus, activation of NKT cells at the time of BMT overcomes the effects of CB, inhibiting the establishment of chimerism and tolerance., (© 2010 The Authors. Journal compilation © 2010 European Society for Organ Transplantation.)
- Published
- 2010
- Full Text
- View/download PDF
32. A sensitive assay for the detection of IgE bound to the major birch pollen allergen, Bet v 1, in the form of immune complexes.
- Author
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Pree I, Reisinger J, Bohle B, Frantal S, Valenta R, and Niederberger V
- Subjects
- Antibodies, Monoclonal immunology, Antigen-Antibody Complex immunology, Enzyme-Linked Immunosorbent Assay, Epitopes immunology, Humans, Immunoblotting, Immunoglobulin E blood, Immunoglobulin E immunology, Plant Proteins immunology, Pollen immunology, Sensitivity and Specificity, Allergens immunology, Antigen-Antibody Complex isolation & purification, Betula immunology, Immunoglobulin E isolation & purification
- Abstract
Allergen-IgE immune complexes, in which the IgE paratopes are occupied by allergen, remain undetected in standard IgE-detection assays which are based on capturing specific IgE by allergens.We describe an assay for the detection of immune complexes consisting of IgE bound to one of the most frequent environmental allergens, the major birch pollen allergen, Bet v 1. This assay is based on a Bet v 1-specific monoclonal antibody, Bip 1, which binds to an epitope on Bet v 1 that is distinct from the epitopes recognized by allergic patients' IgE. IgE-immune complexes formed with sera from birch pollen-allergic patients (n = 46) were undetectable with solid phase-bound allergen but could be captured by Bip 1 immobilized to nitrocellulose membranes or ELISA plates and traced with radioactively or enzymatically labelled anti-human IgE antibodies. The levels of IgE complexed with Bet v 1 measured in our assays were highly correlated with the amounts of non-complexed allergen-specific IgE as determined by the ImmunoCAP assay which is based on solid phase-bound IgE (r = 0.95; p < 0.01). Bet v 1-specific IgE could even be detected at serum dilutions below the cut off of the ImmunoCAP system (i.e., 0.35 kUA/L). We have thus developed a robust and sensitive assay for the detection and quantification of Bet v 1-IgE immune complexes which should be useful to measure allergen-bound IgE in human body fluids and in in vitro experiments.
- Published
- 2009
- Full Text
- View/download PDF
33. Trimolecular complex formation of IgE, Fc epsilon RI, and a recombinant nonanaphylactic single-chain antibody fragment with high affinity for IgE.
- Author
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Lupinek C, Roux KH, Laffer S, Rauter I, Reginald K, Kneidinger M, Blatt K, Ball T, Pree I, Jahn-Schmid B, Allam JP, Novak N, Drescher A, Kricek F, Valent P, Englund H, and Valenta R
- Subjects
- Allergens immunology, Amino Acid Sequence, Anaphylaxis genetics, Anaphylaxis metabolism, Animals, Base Sequence, Basophils immunology, Circular Dichroism, Humans, Immunoglobulin E genetics, Immunoglobulin E metabolism, Immunoglobulin Fab Fragments genetics, Immunoglobulin Fab Fragments metabolism, Immunoglobulin Fragments, Mice, Mice, Inbred BALB C, Molecular Sequence Data, Protein Binding genetics, Protein Binding immunology, Recombinant Proteins biosynthesis, Recombinant Proteins genetics, Recombinant Proteins metabolism, Anaphylaxis immunology, Immunoglobulin E biosynthesis, Immunoglobulin Fab Fragments biosynthesis
- Abstract
IgE is a central molecule in allergic disease. We have isolated cDNAs coding for the heavy and light chains of a murine mAb specific to human IgE and expressed a recombinant single-chain variable fragment (ScFv) derived thereof in Escherichia coli. The purified recombinant ScFv has a molecular mass of 28 kDa as measured by mass spectrometry and shows a beta-sheet fold as determined by circular dichroism. In biosensor-based studies it was demonstrated that the ScFv rapidly and stably binds to human IgE with an affinity of K(D) of 1.52 x 10(-10) M, which is almost as high as the affinity of IgE for FcepsilonRI, and that the ScFv is able to recognize FcepsilonRI-bound IgE and to prevent IgE binding to FcepsilonRI. The ScFv reacts specifically with IgE but not with other isotypes, allows the measurement of allergen-specific IgE in serum samples, and specifically targets cells that contain FcepsilonRI- or FcepsilonRII-bound IgE or that secrete IgE. Using negative-stain electron microscopy we demonstrated the formation of bimolecular complexes consisting of two ScFv molecules and one IgE and trimolecular complexes consisting of IgE, FcepsilonRI, and ScFv in which only one ScFv is able to bind to IgE. Accordingly, we found that the ScFv does not cross-link basophil-bound IgE and hence does not induce histamine release or activation of basophils as demonstrated by FACS analysis of CD203c expression and by histamine release experiments. In vivo skin testing confirmed the lack of allergenic activity of the ScFv. The recombinant ScFv may represent a universal tool for the IgE-targeted treatment of allergies.
- Published
- 2009
- Full Text
- View/download PDF
34. Bone marrow transplantation as a strategy for tolerance induction in the clinic.
- Author
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Pree I, Pilat N, and Wekerle T
- Subjects
- Animals, Chimera, Humans, Immunosuppressive Agents administration & dosage, Mice, Bone Marrow Transplantation immunology, Immune Tolerance
- Abstract
The only way to overcome the need for life-long immunosuppression in a transplant recipient is to induce tolerance. Deletional tolerance can be reliably achieved with the induction of mixed chimerism through transplantation of donor bone marrow (BM). Despite the development of increasingly milder BM transplantation (BMT) animal models, BM engraftment in humans still requires considerably toxic conditioning and puts patients at risk for the development of GVHD. However, in a proof-of-concept trial, mixed chimerism and tolerance have been successfully induced in highly selected patients suffering from both end-stage renal disease and multiple myeloma. Meanwhile, there has been notable progress in developing advanced experimental BMT regimens, in particular through the use of costimulation blockers. Costimulation blockade in rodent models allowed the design of BMT protocols entirely devoid of irradiation. Costimulation blockers have also succeeded in more complex protocols in non-human primates. They are under clinical evaluation in renal transplantation as immunosuppressive therapy. Costimulation blockade may lead the way for the development of milder BMT protocols and broader application of mixed chimerism in organ transplantation.
- Published
- 2009
- Full Text
- View/download PDF
35. Inter-fraction bladder filling variations and time trends for cervical cancer patients assessed with a portable 3-dimensional ultrasound bladder scanner.
- Author
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Ahmad R, Hoogeman MS, Quint S, Mens JW, de Pree I, and Heijmen BJ
- Subjects
- Adult, Dose Fractionation, Radiation, Female, Humans, Organ Size, Time Factors, Tomography, X-Ray Computed, Urinary Bladder anatomy & histology, Uterine Cervical Neoplasms diagnostic imaging, Radiotherapy Planning, Computer-Assisted methods, Ultrasonography instrumentation, Urinary Bladder diagnostic imaging, Uterine Cervical Neoplasms radiotherapy
- Abstract
Background and Purpose: For cervical cancer patients, bladder filling variations may result in inadequate EBRT target coverage, unless large safety margins are used. For a group of patients who received full bladder instructions, inter-fraction variations and time trends in bladder volume were quantified, and a 3D ultrasound (US) scanner was tested for on-line bladder volume measurements., Methods and Materials: For 24 patients, the bladder volume was measured with US at the time of the planning CT scan, and twice weekly during the course of RT. Comparisons of US with planning CT were used to assess the bladder scanner accuracy. Patients were treated in prone on a belly board, EPID images were acquired to correlate set-up errors with bladder filling variations., Results: Measured US and CT bladder volumes were strongly correlated (R = 0.97, slope 1.1 +/- 0.1). The population mean bladder volume at planning of 378 +/- 209 ml (1 SD) reduced to 109 +/- 88 ml (1 SD) in week 6, a reduction by 71% (average reduction 46 ml/week), revealing a large inter-fraction time trend. Intra-patient variation in bladder volume during RT was 168 ml (1 SD) (range 70-266 ml). Rotation around the LR axis was significantly correlated with bladder volume changes., Conclusions: Despite a full bladder instruction, bladder volumes reduced dramatically during treatment, implying large time trends in target position of these patients. The portable US scanner provides a quick and reliable measurement of the bladder volume, which might assist future online treatment adaptation.
- Published
- 2008
- Full Text
- View/download PDF
36. Cardiac metastases.
- Author
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Al-Mamgani A, Baartman L, Baaijens M, de Pree I, Incrocci L, and Levendag PC
- Subjects
- Carcinoma radiotherapy, Heart Neoplasms radiotherapy, Humans, Male, Middle Aged, Palliative Care, Carcinoma secondary, Esophageal Neoplasms pathology, Heart Neoplasms secondary
- Abstract
We report a case of esophageal cancer with symptomatic metastases to the heart; the patient was treated with short-course radiotherapy with good symptomatic relief. We reviewed the current literature regarding the epidemiology, clinical presentation, diagnostic tools, treatment modalities, and the prognosis of cardiac metastases. In this report we summarize the most recent autopsy studies (published between 1975 and 2007), in which we found an autopsy incidence of cardiac metastases of 2.3% among the general population, while the incidence among autopsies of cancer patients was 7.1%. Therefore, we share the opinion with others that there has been an increase in the incidence of cardiac metastases among cancer patients diagnosed after 1970, in comparison with the reported incidences in older series before 1970 (7.1% vs 3.8%; Kruskal-Wallis rank test; P = 0.039). Special attention was given to the role of radiotherapy in the management of cardiac metastases.
- Published
- 2008
- Full Text
- View/download PDF
37. Analysis of epitope-specific immune responses induced by vaccination with structurally folded and unfolded recombinant Bet v 1 allergen derivatives in man.
- Author
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Pree I, Reisinger J, Focke M, Vrtala S, Pauli G, van Hage M, Cromwell O, Gadermaier E, Egger C, Reider N, Horak F, Valenta R, and Niederberger V
- Subjects
- Allergens chemistry, Allergens genetics, Antibody Specificity, Betula genetics, Double-Blind Method, Epitopes genetics, Humans, Immunoglobulin A biosynthesis, Immunoglobulin E biosynthesis, Immunoglobulin G biosynthesis, Immunoglobulin M biosynthesis, Intradermal Tests, Peptide Fragments administration & dosage, Peptide Fragments chemistry, Peptide Fragments genetics, Peptide Fragments immunology, Pollen chemistry, Pollen genetics, Pollen immunology, Protein Engineering, Vaccines, Synthetic chemistry, Allergens administration & dosage, Allergens immunology, Betula immunology, Epitopes administration & dosage, Epitopes immunology, Protein Folding, Vaccines, Synthetic administration & dosage, Vaccines, Synthetic immunology
- Abstract
Previously, we have constructed recombinant derivatives of the major birch pollen allergen, Bet v 1, with a more than 100-fold reduced ability to induce IgE-mediated allergic reactions. These derivatives differed from each other because the two recombinant Bet v 1 fragments represented unfolded molecules whereas the recombinant trimer resembled most of the structural fold of the Bet v 1 allergen. In this study, we analyzed the Ab (IgE, IgG subclass, IgA, IgM) response to Bet v 1, recombinant and synthetic Bet v 1-derived peptides in birch pollen allergic patients who had been vaccinated with the derivatives or adjuvant alone. Furthermore, we studied the induction of IgE-mediated skin responses in these patients using Bet v 1 and Bet v 1 fragments. Both types of vaccines induced a comparable IgG1 and IgG4 response against new sequential epitopes which overlap with the conformational IgE epitopes of Bet v 1. This response was 4- to 5-fold higher than that induced by immunotherapy with birch pollen extract. Trimer more than fragments induced also IgE responses against new epitopes and a transient increase in skin sensitivity to the fragments at the beginning of therapy. However, skin reactions to Bet v 1 tended to decrease one year after treatment in both actively treated groups. We demonstrate that vaccination with folded and unfolded recombinant allergen derivatives induces IgG Abs against new epitopes. These data may be important for the development of therapeutic as well as prophylactic vaccines based on recombinant allergens.
- Published
- 2007
- Full Text
- View/download PDF
38. CTLA4Ig promotes the induction of hematopoietic chimerism and tolerance independently of Indoleamine-2,3-dioxygenase.
- Author
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Pree I, Bigenzahn S, Fuchs D, Koporc Z, Nierlich P, Winkler C, Brandacher G, Sykes M, Muehlbacher F, Langer F, and Wekerle T
- Subjects
- Abatacept, Animals, Immune Tolerance drug effects, Immunosuppressive Agents therapeutic use, Mice, Mice, Inbred BALB C, Transplantation Chimera, Transplantation, Homologous immunology, Whole-Body Irradiation, Bone Marrow Transplantation immunology, Immune Tolerance immunology, Immunoconjugates therapeutic use, Indoleamine-Pyrrole 2,3,-Dioxygenase metabolism
- Abstract
Bone marrow transplantation (BMT) under costimulation blockade induces mixed chimerism and tolerance in rodent models. Recent data, predominantly from in vitro studies, suggest that in addition to blocking the CD28 costimulation pathway CTLA4Ig also acts through upregulating the tryptophan-catabolizing enzyme indoleamine-2,3-dioxygenase (IDO). Here we demonstrate that even though CTLA4Ig is critically required for the induction of chimerism and tolerance in a murine model of nonmyeloablative BMT, IDO activity is not. No significant differences were detectable in the kynurenine to tryptophan ratios (indicative of IDO activity) in sera of BMT recipients treated with CTLA4Ig (tolerant group) versus BMT recipients treated without CTLA4Ig (nontolerant group) versus naïve controls. In vivo inhibition of IDO immediately after BMT with CTLA4Ig or several months thereafter did not block achievement of chimerism and tolerance. Thus, IDO does not play a critical role in the induction or maintenance of chimerism and tolerance in a CTLA4Ig-based BMT model.
- Published
- 2007
- Full Text
- View/download PDF
39. Inducing mixed chimerism and transplantation tolerance through allogeneic bone marrow transplantation with costimulation blockade.
- Author
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Pree I and Wekerle T
- Subjects
- Animals, Transplantation, Homologous methods, Bone Marrow Transplantation immunology, Bone Marrow Transplantation methods, Chimerism, Skin Transplantation methods, Transplantation Tolerance immunology
- Abstract
Induction of mixed chimerism (i.e., coexistence of donor and recipient hematopoietic cells) through transplantation of allogeneic donor bone marrow under appropriate host conditioning, is one of the most reliable strategies to induce transplantation tolerance. Robust tolerance is evident in mixed chimeras as they permanently accept donor skin grafts while promptly rejecting third party grafts. Although historically, myeloablative and T-cell depleting regimens have been described, milder protocols involving costimulation blockade have recently been developed. The prototypical murine protocol described in this chapter, involves the use of CTLA4Ig and a monoclonal antibody-specific for CD154 (CD40L) for costimulation blockade, 3 Gy of nonmyeloablative total body irradiation and a conventional number of 20 x 10(6) fully allogeneic bone marrow cells. Flow cytometry is used to determine levels of multilineage hematopoietic chimerism and deletion of donor-reactive CD4+ T cells. Tolerance is assessed in vivo by grafting of donor and third party skin.
- Published
- 2007
- Full Text
- View/download PDF
40. Recent progress in tolerance induction through mixed chimerism.
- Author
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Pree I, Pilat N, and Wekerle T
- Subjects
- Animals, Humans, Models, Animal, Self Tolerance immunology, Graft Rejection immunology, Graft Rejection prevention & control, Organ Transplantation, Transplantation Chimera immunology, Transplantation Tolerance immunology
- Abstract
Organ transplant recipients require life-long treatment with immunosuppressive drugs. Currently available immunosuppression is associated with substantial morbidity and mortality, and is ineffective in inhibiting chronic rejection and graft loss. Therefore, a permanent state of donor-specific tolerance remains a primary goal for transplantation research. The induction of mixed hematopoietic chimerism is an attractive concept in this regard. Hematopoietic chimerism modulates the immunologic repertoire by extending the mechanisms of self-tolerance to donor-specific allotolerance. Despite recent progress in developing nontoxic bone marrow transplantation protocols for rodents, translation to large animals has remained difficult. Here, we outline the concept of tolerance via mixed chimerism, and review recent progress and remaining challenges in bringing this approach to the clinical setting., (2007 S. Karger AG, Basel)
- Published
- 2007
- Full Text
- View/download PDF
41. The role of non-deletional tolerance mechanisms in a murine model of mixed chimerism with costimulation blockade.
- Author
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Bigenzahn S, Blaha P, Koporc Z, Pree I, Selzer E, Bergmeister H, Wrba F, Heusser C, Wagner K, Muehlbacher F, and Wekerle T
- Subjects
- Animals, Antibodies, Monoclonal administration & dosage, CD4-Positive T-Lymphocytes immunology, CD40 Ligand immunology, Female, Graft Rejection immunology, Humans, Mice, Mice, Inbred BALB C, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, SCID, Skin Transplantation immunology, Bone Marrow Transplantation immunology, CD40 Ligand physiology, Clonal Deletion immunology, Graft Survival immunology, Immune Tolerance physiology, Interleukin-2 antagonists & inhibitors, Transplantation Chimera immunology
- Abstract
Peripheral and central clonal deletion are important tolerance mechanisms in models using bone marrow transplantation (BMT) with costimulation blockade (CB). However, since tolerance can be found before peripheral deletion is complete and since elimination of recipient CD4(+) cells at the time of BMT prevents tolerance induction, we investigated the potential roles of regulation and anergy in such a murine model. We found that transient elimination of CD25(+) cells or neutralization of IL2 immediately after BMT and CB prevented the induction of skin graft tolerance. Cotransfer into SCID mice of CD4(+) cells taken from chimeras early after BMT, together with naive recipient-type CD4(+) cells significantly prolonged donor skin graft survival. In contrast, cotransfer of CD4(+) cells harvested from chimeras late after BMT did not prolong donor skin graft survival. Besides, depletion of CD25(+) cells in established chimeras several months post-BMT did not break tolerance. In vivo administration of recombinant IL2 inhibited chimerism and tolerance neither early nor late post-BMT, arguing against a decisive role for classical anergy. Thus, CD4 cell-mediated regulation contributes significantly to tolerance induction early after BMT, but appears to have no critical role in the maintenance of tolerance.
- Published
- 2005
- Full Text
- View/download PDF
42. [1901-2001: 100 years of physicians of infant and toddler welfare centers in the Netherlands].
- Author
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de Pree-Geerlings B, de Pree IM, and Bulk-Bunschoten AM
- Subjects
- Child Health Services organization & administration, Child, Preschool, Health Policy history, History, 20th Century, Humans, Infant, Infant Welfare trends, Infant, Newborn, Netherlands, Pediatrics history, Child Health Services history, Infant Welfare history
- Abstract
This year marks the centenary of infant welfare centres in the Netherlands. In 1901, Plantenga opened the first infant welfare centre in The Hague, the Netherlands. Initially, only advice about feeding was given and the growth of the infant was monitored. To support mothers, extra milk was supplied in so-called 'milk kitchens'. Over the years the tasks have been extended to include a wide range of preventive measures. At first the doctors in infant welfare clinics were predominantly paediatricians but later general practitioners and doctors specialised in infant primary health care followed. In their 100-years existence, infant welfare clinics have grown into an intricate network which sees 98% of Dutch infants.
- Published
- 2001
43. [Squamous cell carcinoma of the nail bed].
- Author
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de Pree IM, van de Sandt MM, and Nagy TO
- Subjects
- Aged, Aged, 80 and over, Amputation, Surgical, Bowen's Disease surgery, Carcinoma, Squamous Cell surgery, Diagnostic Errors, Female, Fingers surgery, Humans, Nail Diseases surgery, Neoplasms, Multiple Primary surgery, Paronychia diagnosis, Skin Neoplasms surgery, Treatment Outcome, Bowen's Disease diagnosis, Carcinoma, Squamous Cell diagnosis, Nail Diseases diagnosis, Neoplasms, Multiple Primary diagnosis, Skin Neoplasms diagnosis
- Abstract
A 85-year-old woman presented clinically with paronychia. Treatment for this was uneffective, however. Finally, the diagnosis was Bowen's disease of the nail bed with underlying invasive squamous cell carcinoma. Treatment consisted of a subcapital amputation through the middle phalanx. Subungual tumors often appear to be a diagnostic problem because of their benign presentation. Every longstanding nail bed disease that does not respond to therapy needs to be biopted.
- Published
- 1999
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