27 results on '"Nienhuis PH"'
Search Results
2. Wax and wane of eelgrass Zostera marina and water column silicon levels
- Author
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Herman, PMJ, primary, Hemminga, MA, additional, Nienhuis, PH, additional, Verschuure, JM, additional, and Wessel, EGJ, additional
- Published
- 1996
- Full Text
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3. Consumption of eelgrass (Zostera marina) by birds and invertebrates: an annual budget
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Nienhuis, PH, primary and Groenendijk, AM, additional
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- 1986
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4. A Simulation Model of Production, Seasonal Changes in Biomass and Distribution of Eelgrass (Zostera marina) in Lake Grevelingen
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Verhagen, JHG, primary and Nienhuis, PH, additional
- Published
- 1983
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5. Advances in PET Imaging of Large Vessel Vasculitis: An Update and Future Trends.
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van der Geest KSM, Gheysens O, Gormsen LC, Glaudemans AWJM, Tsoumpas C, Brouwer E, Nienhuis PH, van Praagh GD, and Slart RHJA
- Subjects
- Humans, Vasculitis diagnostic imaging, Positron-Emission Tomography methods
- Abstract
Systemic vasculitides are autoimmune diseases characterized by inflammation of blood vessels. They are categorized based on the size of the preferentially affected blood vessels: large-, medium-, and small-vessel vasculitides. The main forms of large-vessel vasculitis include giant cell arteritis (GCA) and Takayasu arteritis (TAK). Depending on the location of the affected vessels, various imaging modalities can be employed for diagnosis of large vessel vasculitis: ultrasonography (US), magnetic resonance angiography (MRA), computed tomography angiography (CTA), and [
18 F]-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT). These imaging tools offer complementary information about vascular changes occurring in vasculitis. Recent advances in PET imaging in large vessel vasculitis include the introduction of digital long axial field-of-view PET/CT, dedicated acquisition, quantitative methodologies, and the availability of novel radiopharmaceuticals. This review aims to provide an update on the current status of PET imaging in large vessel vasculitis and to share the latest developments on imaging vasculitides., 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 Inc. All rights reserved.)- Published
- 2024
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6. Altered Plasma Levels and Tissue Expression of Fibroblast Activation Protein Alpha in Giant Cell Arteritis.
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Xu S, Jiemy WF, Boots AMH, Arends S, van Sleen Y, Nienhuis PH, van der Geest KSM, Heeringa P, Brouwer E, and Sandovici M
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- Humans, Male, Female, Aged, Middle Aged, Fibroblasts metabolism, Aged, 80 and over, Temporal Arteries pathology, Temporal Arteries metabolism, Case-Control Studies, Biomarkers blood, Giant Cell Arteritis blood, Giant Cell Arteritis metabolism, Giant Cell Arteritis pathology, Endopeptidases blood, Serine Endopeptidases blood, Serine Endopeptidases metabolism, Gelatinases blood, Gelatinases metabolism, Membrane Proteins blood, Membrane Proteins metabolism
- Abstract
Objective: Giant cell arteritis (GCA) is characterized by granulomatous inflammation of the medium- and large-sized arteries accompanied by remodeling of the vessel wall. Fibroblast activation protein alpha (FAP) is a serine protease that promotes both inflammation and fibrosis. Here, we investigated the plasma levels and vascular expression of FAP in GCA., Methods: Plasma FAP levels were measured with enzyme-linked immunosorbent assay in treatment-naive patients with GCA (n = 60) and polymyalgia rheumatica (PMR) (n = 63) compared with age- and sex-matched healthy controls (HCs) (n = 42) and during follow-up, including treatment-free remission (TFR). Inflamed temporal artery biopsies (TABs) of patients with GCA (n = 9), noninflamed TABs (n = 14), and aorta samples from GCA-related (n = 9) and atherosclerosis-related aneurysm (n = 11) were stained for FAP using immunohistochemistry. Immunofluorescence staining was performed for fibroblasts (CD90), macrophages (CD68/CD206/folate receptor beta), vascular smooth muscle cells (desmin), myofibroblasts (α-smooth muscle actin), interleukin-6 (IL-6), and matrix metalloproteinase-9 (MMP-9)., Results: Baseline plasma FAP levels were significantly lower in patients with GCA compared with patients with PMR and HCs and inversely correlated with systemic markers of inflammation and angiogenesis. FAP levels decreased even further at 3 months on remission in patients with GCA and gradually increased to the level of HCs in TFR. FAP expression was increased in inflamed TABs and aorta of patients with GCA compared with control tissues. FAP was abundantly expressed in fibroblasts and macrophages. Some of the FAP
+ fibroblasts expressed IL-6 and MMP-9., Conclusion: FAP expression in GCA is clearly modulated both in plasma and in vessels. FAP may be involved in the inflammatory and remodeling processes in GCA and have utility as a target for imaging and therapeutic intervention., (© 2024 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)- Published
- 2024
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7. Improved Diagnostic Accuracy for Polymyalgia Rheumatica using FDG-PET/CT with Clinical Diagnosis or 2012 ACR/EULAR Classification Criteria.
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Nielsen AW, van der Geest KSM, Hansen IT, Nielsen BD, Kjær SG, Blegvad-Nissen J, Nienhuis PH, Sandovici M, Rewers K, Møller Sørensen C, Slart RHJA, Gormsen LC, Brouwer E, Hauge EM, and Keller KK
- Abstract
Purpose: In routine care, clinicians may employ 2-[18F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) computed tomography (CT) to validate their initial clinical diagnosis of polymyalgia rheumatica (PMR). Nevertheless, the diagnostic utility of combining FDG-PET/CT findings with clinical presentation has not been explored. Therefore, this study aimed to investigate whether the diagnostic accuracy for PMR could be enhanced by combining FDG-PET/CT findings with the clinical baseline diagnosis or the 2012 ACR/EULAR clinical classification criteria for PMR., Methods: An investigation and a validation cohort were included from two countries, encompassing 66/27 and 36/21 PMR/non-PMR patients, respectively. The cohorts comprised treatment-naïve patients suspected of PMR, who initially received a clinical baseline diagnosis and underwent FDG-PET/CT scans. The FDG-PET/CT Leuven-score was applied to classify patients as either PMR or non-PMR and combined with the clinical baseline diagnosis. Final diagnoses were established through clinical follow-up after twelve or six months in the investigation and validation cohorts, respectively., Results: In the investigation cohort, a clinical baseline diagnosis yielded a sensitivity/specificity of 94%/82%, compared with 78%/70% using the ACR/EULAR criteria. Combining the clinical baseline diagnosis with a positive Leuven-score showed a sensitivity/specificity of 80%/93%, compared with 80%/82% for an ACR/EULAR-Leuven-score. In the validation cohort, the baseline diagnosis revealed a sensitivity/specificity of 100%/91%, compared with 92%/76% using the ACR/EULAR criteria. Combining FDG-PET/CT with the baseline diagnosis demonstrated a sensitivity/specificity of 83%/95% compared with 89%/81% for the ACR/EULAR-Leuven-score., Conclusion: Combining FDG-PET/CT findings with the clinical baseline diagnosis or ACR/EULAR clinical classification criteria can improve the diagnostic specificity for PMR., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2024
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8. Multimodality imaging to assess diagnosis and evaluate complications of large vesselarteritis.
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Aghayev A, Weber B, Lins de Carvalho T, Glaudemans AWJM, Nienhuis PH, van der Geest KSM, and Slart RHJA
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- Humans, Multimodal Imaging methods, Giant Cell Arteritis diagnostic imaging, Giant Cell Arteritis complications, Takayasu Arteritis diagnostic imaging, Takayasu Arteritis complications
- Abstract
Different types of vasculitis can be distinguished according to the blood vessel's size that is preferentially affected: large-vessel, medium-vessel, and small-vessel vasculitides. Giant cell arteritis (GCA) and Takayasu's arteritis (TAK) are the main forms of large-vessel vasculitis, and may lead to lumen narrowing. Clinical manifestations of arterial narrowing on the short- and long term include vision loss, stroke, limb ischemia, and heart failure. Imaging tools are well established diagnostic tests for large-vessel vasculitis and may aid therapy monitoring in selected cases while providing important information regarding the occurrence of vascular damage, tissue and organ complications. This review aims to provide the current status of multimodality imaging for the diagnosis and identification of vascular complications in the field of large vessel vasculitis., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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9. Automated multiclass segmentation, quantification, and visualization of the diseased aorta on hybrid PET/CT-SEQUOIA.
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van Praagh GD, Nienhuis PH, Reijrink M, Davidse MEJ, Duff LM, Spottiswoode BS, Mulder DJ, Prakken NHJ, Scarsbrook AF, Morgan AW, Tsoumpas C, Wolterink JM, Mouridsen KB, Borra RJH, Sinha B, and Slart RHJA
- Subjects
- Humans, Aorta diagnostic imaging, Aortic Diseases diagnostic imaging, Female, Feasibility Studies, Male, Positron Emission Tomography Computed Tomography, Image Processing, Computer-Assisted methods, Automation
- Abstract
Background: Cardiovascular disease is the most common cause of death worldwide, including infection and inflammation related conditions. Multiple studies have demonstrated potential advantages of hybrid positron emission tomography combined with computed tomography (PET/CT) as an adjunct to current clinical inflammatory and infectious biochemical markers. To quantitatively analyze vascular diseases at PET/CT, robust segmentation of the aorta is necessary. However, manual segmentation is extremely time-consuming and labor-intensive., Purpose: To investigate the feasibility and accuracy of an automated tool to segment and quantify multiple parts of the diseased aorta on unenhanced low-dose computed tomography (LDCT) as an anatomical reference for PET-assessed vascular disease., Methods: A software pipeline was developed including automated segmentation using a 3D U-Net, calcium scoring, PET uptake quantification, background measurement, radiomics feature extraction, and 2D surface visualization of vessel wall calcium and tracer uptake distribution. To train the 3D U-Net, 352 non-contrast LDCTs from (2-[
18 F]FDG and Na[18 F]F) PET/CTs performed in patients with various vascular pathologies with manual segmentation of the ascending aorta, aortic arch, descending aorta, and abdominal aorta were used. The last 22 consecutive scans were used as a hold-out internal test set. The remaining dataset was randomly split into training (n = 264; 80%) and validation (n = 66; 20%) sets. Further evaluation was performed on an external test set of 49 PET/CTs. The dice similarity coefficient (DSC) and Hausdorff distance (HD) were used to assess segmentation performance. Automatically obtained calcium scores and uptake values were compared with manual scoring obtained using clinical softwares (syngo.via and Affinity Viewer) in six patient images. intraclass correlation coefficients (ICC) were calculated to validate calcium and uptake values., Results: Fully automated segmentation of the aorta using a 3D U-Net was feasible in LDCT obtained from PET/CT scans. The external test set yielded a DSC of 0.867 ± 0.030 and HD of 1.0 [0.6-1.4] mm, similar to an open-source model with a DSC of 0.864 ± 0.023 and HD of 1.4 [1.0-1.8] mm. Quantification of calcium and uptake values were in excellent agreement with clinical software (ICC: 1.00 [1.00-1.00] and 0.99 [0.93-1.00] for calcium and uptake values, respectively)., Conclusions: We present an automated pipeline to segment the ascending aorta, aortic arch, descending aorta, and abdominal aorta on LDCT from PET/CT and to accurately provide uptake values, calcium scores, background measurement, radiomics features, and a 2D visualization. We call this algorithm SEQUOIA (SEgmentation, QUantification, and visualizatiOn of the dIseased Aorta) and is available at https://github.com/UMCG-CVI/SEQUOIA. This model could augment the utility of aortic evaluation at PET/CT studies tremendously, irrespective of the tracer, and potentially provide fast and reliable quantification of cardiovascular diseases in clinical practice, both for primary diagnosis and disease monitoring., (© 2024 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)- Published
- 2024
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10. Comparing Diagnostic Performance of Short and Long [ 18 F]FDG-PET Acquisition Times in Giant Cell Arteritis.
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Nienhuis PH, van Nieuwland M, van Praagh GD, Markusiewicz K, Colin EM, van der Geest KSM, Wagenaar N, Brouwer E, Alves C, and Slart RHJA
- Abstract
(1) Background: In giant cell arteritis (GCA), the assessment of cranial arteries using [
18 F]fluorodeoxyglucose ([18 F]FDG) positron emission tomography (PET) combined with low-dose computed tomography (CT) may be challenging due to low image quality. This study aimed to investigate the effect of prolonged acquisition time on the diagnostic performance of [18 F]FDG PET/CT in GCA. (2) Methods: Patients with suspected GCA underwent [18 F]FDG-PET imaging with a short acquisition time (SAT) and long acquisition time (LAT). Two nuclear medicine physicians (NMPs) reported the presence or absence of GCA according to the overall image impression (gestalt) and total vascular score (TVS) of the cranial arteries. Inter-observer agreement and intra-observer agreement were assessed. (3) Results: In total, 38 patients were included, of whom 20 were diagnosed with GCA and 18 were without it. Sensitivity and specificity for GCA on SAT scans were 80% and 72%, respectively, for the first NMP, and 55% and 89% for the second NMP. On the LAT scans, these values were 65% and 83%, and 75% and 83%, respectively. When using the TVS, LAT scans showed especially increased specificity (94% for both NMPs). Observer agreement was higher on the LAT scans compared with that on the SAT scan. (4) Conclusions: LAT combined with the use of the TVS may decrease the number of false-positive assessments of [18 F]FDG PET/CT. Additionally, LAT and TVS may increase both inter and intra-observer agreement.- Published
- 2023
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11. The clinical value of quantitative cardiovascular molecular imaging: a step towards precision medicine.
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Tingen HSA, van Praagh GD, Nienhuis PH, Tubben A, van Rijsewijk ND, Ten Hove D, Mushari NA, Martinez-Lucio TS, Mendoza-Ibañez OI, van Sluis J, Tsoumpas C, Glaudemans AWJM, and Slart RHJA
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- Humans, Precision Medicine, Heart, Tomography, Emission-Computed, Single-Photon methods, Radiopharmaceuticals, Positron-Emission Tomography methods, Cardiovascular Diseases diagnostic imaging
- Abstract
Cardiovascular diseases (CVD) are the leading cause of death worldwide and have an increasing impact on society. Precision medicine, in which optimal care is identified for an individual or a group of individuals rather than for the average population, might provide significant health benefits for this patient group and decrease CVD morbidity and mortality. Molecular imaging provides the opportunity to assess biological processes in individuals in addition to anatomical context provided by other imaging modalities and could prove to be essential in the implementation of precision medicine in CVD. New developments in single-photon emission computed tomography (SPECT) and positron emission tomography (PET) systems, combined with rapid innovations in promising and specific radiopharmaceuticals, provide an impressive improvement of diagnostic accuracy and therapy evaluation. This may result in improved health outcomes in CVD patients, thereby reducing societal impact. Furthermore, recent technical advances have led to new possibilities for accurate image quantification, dynamic imaging, and quantification of radiotracer kinetics. This potentially allows for better evaluation of disease activity over time and treatment response monitoring. However, the clinical implementation of these new methods has been slow. This review describes the recent advances in molecular imaging and the clinical value of quantitative PET and SPECT in various fields in cardiovascular molecular imaging, such as atherosclerosis, myocardial perfusion and ischemia, infiltrative cardiomyopathies, systemic vascular diseases, and infectious cardiovascular diseases. Moreover, the challenges that need to be overcome to achieve clinical translation are addressed, and future directions are provided.
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- 2023
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12. Salivary gland 18F-FDG-PET/CT uptake patterns in Sjögren's syndrome and giant cell arteritis patients.
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Grootelaar RGJ, van Ginkel MS, Nienhuis PH, Arends S, Pieterman RM, Brouwer E, Bootsma H, Glaudemans AWJM, and Slart RHJA
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- Humans, Fluorodeoxyglucose F18, Positron Emission Tomography Computed Tomography, Salivary Glands diagnostic imaging, Parotid Gland diagnostic imaging, Submandibular Gland, Sjogren's Syndrome diagnostic imaging, Giant Cell Arteritis diagnostic imaging, Lung Neoplasms
- Abstract
Objectives: Wide variety in salivary gland 18F-FDG-uptake is observed in the general population. A general consensus about the usefulness of 18F-FDG-PET/CT to detect salivary gland inflammatory conditions, such as in primary Sjögren's syndrome (pSS), is not yet clear. This study aimed to investigate whether there are differences in uptake of 18F-FDG in salivary glands among two autoimmune groups [pSS, giant cell arteritis (GCA)] and a non-autoimmune group (lung cancer)., Methods: PSS patients aged ≥50 years who underwent 18F-FDG-PET/CT were included and age-matched with GCA patients and a non-autoimmune control group (lung cancer patients). Scans were visually evaluated and quantitative analysis was performed by measuring standardised uptake values (SUV) within salivary glands and lacrimal glands. For GCA patients, arteries in the vicinity of the parotid and submandibular gland were assessed for positivity., Results: PSS patients did not show increased 18F-FDG-uptake in the parotid or submandibular gland, compared to the other two groups. For the tubarial gland, significantly higher SUVmax was found in the pSS patient group. Interestingly, GCA patients had significantly higher SUVmax in the submandibular gland than the other two groups. Visual 18F-FDG-positivity of cranial arteries related to the parotid and submandibular glands was associated with significantly higher SUVmax in salivary glands of GCA patients., Conclusions: Although 18F-FDG-uptake was not increased in parotid and submandibular glands of pSS patients, increased 18F-FDG-uptake in tubarial glands of pSS patients might indicate a role for these glands in pSS. Furthermore, parotid and submandibular glands may be affected by local vasculitis in GCA.
- Published
- 2023
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13. Role of 18 F-FDG PET/CT in Large Vessel Vasculitis and Polymyalgia Rheumatica.
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Slart RHJA, Nienhuis PH, Glaudemans AWJM, Brouwer E, Gheysens O, and van der Geest KSM
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- Humans, Positron Emission Tomography Computed Tomography, Fluorodeoxyglucose F18 therapeutic use, Positron-Emission Tomography, Giant Cell Arteritis diagnostic imaging, Giant Cell Arteritis drug therapy, Polymyalgia Rheumatica diagnostic imaging, Polymyalgia Rheumatica drug therapy
- Abstract
Systemic vasculitides comprise a group of autoimmune diseases affecting blood vessels, including large vessel vasculitis (LVV) and medium-sized vessel vasculitis such as giant cell arteritis (GCA) and Takayasu arteritis (TAK). GCA frequently overlaps with polymyalgia rheumatica (PMR), a rheumatic inflammatory condition affecting bursae, tendons or tendon sheaths, and joints.
18 F-FDG PET/CT plays an important role in the diagnostic work-up of GCA, PMR, and TAK and is increasingly used to monitor treatment response. This continuing education article provides up-to-date guidance on the role of18 F-FDG PET/CT in patients with LVV, medium-sized vessel vasculitis, and PMR. It provides a general introduction on the clinical presentation and challenges in the diagnostic work-up of LVV and medium-sized vessel vasculitis, with a focus on the 2 major LVV subtypes: GCA, including PMR, and TAK. Next, practice points to perform and interpret the results of18 F-FDG PET/CT are described in line with the published procedure recommendations. Furthermore, the diagnostic performance and its role for treatment monitoring are discussed, taking into account recent international recommendations for the use of imaging in LVV and medium-sized vessel vasculitis in clinical practice. This is illustrated by several clinically representative PET/CT scan examples. Lastly, knowledge of limitations and pitfalls is essential to understand the role of18 F-FDG PET/CT in LVV, medium-sized vessel vasculitis, and PMR. Challenges and opportunities, as well as future research and conclusions, are highlighted. Learning objectives provide up-to-date guidance for the role of18 F-FDG PET/CT in patients with suspected LVV, medium-sized vessel vasculitis, and PMR., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)- Published
- 2023
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14. A Case of Clinical Uncertainty Solved: Giant Cell Arteritis with Polymyalgia Rheumatica Swiftly Diagnosed with Long Axial Field of View PET.
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Nienhuis PH, van Sluis J, van Snick JH, Glaudemans AWJM, Meijering S, Brouwer E, and Slart RHJA
- Abstract
The clinical presentation of giant cell arteritis (GCA) is often nonspecific. Differentiating GCA from infectious, malignant, or other autoimmune pathology based on signs, symptoms, and laboratory parameters may therefore be difficult. Fluorine-18-fluorodeoxyglucose (
18 F-FDG) positron emission tomography/computed tomography (PET/CT) imaging is an established tool in the diagnostic workup of GCA. An advantage of18 F-FDG-PET/CT is its ability to assist in the differential diagnosis by being able to demonstrate infection, inflammation, and malignancy when used in conjunction with clinical and laboratory data. Downsides to the use of18 F-FDG-PET/CT include its relatively low spatial resolution, associated radiation exposure, and the relatively long duration of imaging, causing limited availability and patient inconvenience. The advent of long axial field-of-view (LAFOV) PET/CT systems allows for PET imaging at a reduced imaging time or reduced tracer dose while maintaining high image quality. Here, we provide the first reported case of a patient with GCA and polymyalgia rheumatica (PMR) diagnosed using LAFOV PET/CT imaging. The patient presented in this case report had already been experiencing nonspecific symptoms for several years for which no cause was found. Lab investigations showed increased inflammatory parameters as well as persistent anemia.18 F-FDG LAFOV PET/CT attained high-quality images with clear signs of GCA and PMR even at 1 min of scan duration.- Published
- 2022
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15. The Summer School Oncology Groningen: Improving a Successful International Course by Refining the Old, Maintaining What's Good.
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Boske ECE, Nienhuis PH, Hammer C, Jalving M, Kruyt FAE, de Vries J, Roodenburg JLN, Metman MJH, and Kruijff S
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- Curriculum, Humans, Medical Oncology education, Netherlands, Schools, Neoplasms therapy, Students, Medical
- Abstract
For more than two decades, the International Summer School Oncology for Medical Students (ISOMS) has organized a biennial 2-week international summer school program in Groningen, the Netherlands. The summer school aims to increase knowledge about general cancer care, reduce fear of talking to cancer patients, and expose students to cancer-related problems. After 22 years, there was a need to improve the summer school format, the application procedure, and the intensity of the course. Here, we describe and evaluate these and additional changes that were made to the program. Several changes were made to the summer school format. The course was shortened from 10 days to a more intensive 7 days. The scientific program was integrated with the clinical program and students were taught scientific writing and presentation skills. The application process involved a personal video pitch. Importantly, the new summer school format was organized by a committee in which medical students had the lead. To evaluate the changes to the summer school, we conducted knowledge tests and regularly obtained feedback. There was a high overall student satisfaction, with a median score of a 9 out of 10. Students appreciated the interactive sessions and practicals and the scientific program, and were satisfied with the course level. All students had improved test scores. Improvement points highlighted the need for a less packed schedule and more lectures on basic oncology principles, or were related to specific lectures. The student-led innovation and adaptation of the ISOMS has been successful., (© 2021. The Author(s).)
- Published
- 2022
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16. Comment on: Plasma Pyruvate Kinase M2 as a marker of vascular inflammation in giant cell arteritis: reply.
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Esen I, Jiemy WF, van Sleen Y, Reitsema RD, Bijzet J, de Jong DM, Nienhuis PH, Slart RHJA, Heeringa P, Boots AMH, and Brouwer E
- Subjects
- Biomarkers, Humans, Inflammation, Pyruvate Kinase blood, Giant Cell Arteritis diagnosis
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- 2022
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17. Plasma Pyruvate Kinase M2 as a marker of vascular inflammation in giant cell arteritis.
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Esen I, Jiemy WF, van Sleen Y, Bijzet J, de Jong DM, Nienhuis PH, Slart RHJA, Heeringa P, Boots AMH, and Brouwer E
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- Biomarkers blood, Chitinase-3-Like Protein 1, Fluorodeoxyglucose F18, Humans, Inflammation, Leukocyte L1 Antigen Complex, Positron Emission Tomography Computed Tomography, Pyruvate Kinase, Thyroid Hormone-Binding Proteins, Carrier Proteins blood, Giant Cell Arteritis diagnostic imaging, Giant Cell Arteritis pathology, Membrane Proteins blood, Thyroid Hormones blood
- Abstract
Objectives: GCA is a large vessel vasculitis in which metabolically active immune cells play an important role. GCA diagnosis is based on CRP/ESR and temporal artery biopsies (TABs), in combination with 18F-fluorodeoxyglucose ([18F]FDG)-PET/CT relying on enhanced glucose uptake by glycolytic macrophages. Here, we studied circulating Pyruvate Kinase M2 (PKM2), a glycolytic enzyme, as a possible systemic marker of vessel wall inflammation in GCA., Methods: Immunohistochemical detection of PKM2 was performed on inflamed (n = 12) and non-inflamed (n = 4) TABs from GCA patients and non-GCA (n = 9) patients. Dimeric PKM2 levels were assessed in plasma of GCA patients (n = 44), age-matched healthy controls (n = 41), metastatic melanoma patients (n = 7) and infection controls (n = 11). CRP, ESR and macrophage markers calprotectin and YKL-40 were correlated with plasma PKM2 levels. To detect the cellular source of plasma PKM2 in tissue, double IF staining was performed on inflamed GCA TABs. [18F]FDG-PET scans of 23 GCA patients were analysed and maximum standard uptake values and target to background ratios were calculated., Results: PKM2 is abundantly expressed in TABs of GCA patients. Dimeric PKM2 plasma levels were elevated in GCA and correlated with CRP, ESR, calprotectin and YKL-40 levels. Elevated plasma PKM2 levels were downmodulated by glucocorticoid treatment. PKM2 was detected in both macrophages and T cells at the site of vascular inflammation. Circulating PKM2 levels correlated with average target to background ratios PET scores., Conclusion: Elevated plasma PKM2 levels reflect active vessel inflammation in GCA and may assist in disease diagnosis and in disease monitoring., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)
- Published
- 2022
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18. Novel PET Imaging of Inflammatory Targets and Cells for the Diagnosis and Monitoring of Giant Cell Arteritis and Polymyalgia Rheumatica.
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van der Geest KSM, Sandovici M, Nienhuis PH, Slart RHJA, Heeringa P, Brouwer E, and Jiemy WF
- Abstract
Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are two interrelated inflammatory diseases affecting patients above 50 years of age. Patients with GCA suffer from granulomatous inflammation of medium- to large-sized arteries. This inflammation can lead to severe ischemic complications (e.g., irreversible vision loss and stroke) and aneurysm-related complications (such as aortic dissection). On the other hand, patients suffering from PMR present with proximal stiffness and pain due to inflammation of the shoulder and pelvic girdles. PMR is observed in 40-60% of patients with GCA, while up to 21% of patients suffering from PMR are also affected by GCA. Due to the risk of ischemic complications, GCA has to be promptly treated upon clinical suspicion. The treatment of both GCA and PMR still heavily relies on glucocorticoids (GCs), although novel targeted therapies are emerging. Imaging has a central position in the diagnosis of GCA and PMR. While [
18 F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) has proven to be a valuable tool for diagnosis of GCA and PMR, it possesses major drawbacks such as unspecific uptake in cells with high glucose metabolism, high background activity in several non-target organs and a decrease of diagnostic accuracy already after a short course of GC treatment. In recent years, our understanding of the immunopathogenesis of GCA and, to some extent, PMR has advanced. In this review, we summarize the current knowledge on the cellular heterogeneity in the immunopathology of GCA/PMR and discuss how recent advances in specific tissue infiltrating leukocyte and stromal cell profiles may be exploited as a source of novel targets for imaging. Finally, we discuss prospective novel PET radiotracers that may be useful for the diagnosis and treatment monitoring in GCA and PMR., Competing Interests: KG has received a speaker fee from Roche paid to the UMCG. EB has received consultancy and speaker fees from Roche paid to the UMCG. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 van der Geest, Sandovici, Nienhuis, Slart, Heeringa, Brouwer and Jiemy.)- Published
- 2022
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19. 18 F-BMS986192 PET Imaging of PD-L1 in Metastatic Melanoma Patients with Brain Metastases Treated with Immune Checkpoint Inhibitors: A Pilot Study.
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Nienhuis PH, Antunes IF, Glaudemans AWJM, Jalving M, Leung D, Noordzij W, Slart RHJA, de Vries EFJ, and Hospers GAP
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- B7-H1 Antigen, Fluorodeoxyglucose F18 therapeutic use, Humans, Immune Checkpoint Inhibitors, Pilot Projects, Positron Emission Tomography Computed Tomography methods, Positron-Emission Tomography, Brain Neoplasms diagnostic imaging, Brain Neoplasms drug therapy, Melanoma diagnostic imaging, Melanoma drug therapy, Neoplasms, Second Primary
- Abstract
Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) frequently induces tumor response in metastatic melanoma patients. However, tumor response often takes months and may be heterogeneous. Consequently, additional local treatment for nonresponsive metastases may be needed, especially in the case of brain metastases. Noninvasive imaging may allow the characterization of (brain) metastases to predict response. This pilot study uses
18 F-BMS986192 PET for PD-L1 expression to explore the variability in metastatic tracer uptake and its relation to tumor response, with a special focus on brain metastases. Methods: Metastatic melanoma patients underwent whole-body18 F-BMS986192 PET/CT scanning before and 6 wk after starting ICI therapy.18 F-BMS986192 uptake was measured in healthy tissues, organs, and tumor lesions. Tumor response was evaluated at 12 wk using CT of the thorax/abdomen and MRI of the brain. RECIST, version 1.1, was used to define therapy response per patient. Response per lesion was measured by the percentage change in lesion diameter. Toxicity was assessed according to Common Terminology Criteria for Adverse Events, version 4.0. Results: Baseline18 F-BMS986192 PET/CT was performed in 8 patients, with follow-up scans in 4 patients. The highest tracer uptake was observed in the spleen, bone marrow, kidneys, and liver. Tracer uptake in tumor lesions was heterogeneous. In total, 42 tumor lesions were identified at baseline, with most lesions in the lungs ( n = 21) and brain ( n = 14). Tracer uptake was similar between tumor locations.18 F-BMS986192 uptake in lesions at baseline, corrected for blood-pool activity, was negatively correlated with the change lesion diameter at response evaluation (r = -0.49, P = 0.005), both in intra- and extracerebral lesions. Receiver-operating-characteristic analysis demonstrated that18 F-BMS986192 uptake can discriminate between responding and nonresponding lesions with an area under the curve of 0.82. At the follow-up scan, an increased18 F-BMS986192 uptake compared with baseline scan was correlated with an increased lesion diameter at response evaluation. In the follow-up18 F-BMS986192 PET scan of 2 patients, ICI-related toxicity (thyroiditis and colitis) was detected. Conclusion: In this pilot study,18 F-BMS986192 PET showed heterogeneous uptake in intra- and extracerebral metastatic lesions in melanoma patients. Baseline18 F-BMS986192 uptake was able to predict an ICI treatment-induced reduction in lesion volume, whereas the follow-up PET scan allowed the detection of treatment-induced toxicity., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)- Published
- 2022
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20. Limitations and Pitfalls of FDG-PET/CT in Infection and Inflammation.
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Pijl JP, Nienhuis PH, Kwee TC, Glaudemans AWJM, Slart RHJA, and Gormsen LC
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- Humans, Inflammation diagnostic imaging, Positron-Emission Tomography, Fluorodeoxyglucose F18, Positron Emission Tomography Computed Tomography
- Abstract
White blood cells activated by either a pathogen or as part of a systemic inflammatory disease are characterized by high energy consumption and are therefore taking up the glucose analogue PET tracer FDG avidly. It is therefore not surprising that a steadily growing body of research and clinical reports now supports the use of FDG PET/CT to diagnose a wide range of patients with non-oncological diseases. However, using FDG PET/CT in patients with infectious or inflammatory diseases has some limitations and potential pitfalls that are not necessarily as pronounced in oncology FDG PET/CT. Some of these limitations are of a general nature and related to the laborious acquisition of PET images in patients that are often acutely ill, whereas others are more disease-specific and related to the particular metabolism in some of the organs most commonly affected by infections or inflammatory disease. Both inflammatory and infectious diseases are characterized by a more diffuse and less pathognomonic pattern of FDG uptake than oncology FDG PET/CT and the affected organs also typically have some physiological FDG uptake. In addition, patients referred to PET/CT with suspected infection or inflammation are rarely treatment naïve and may have received varying doses of antibiotics, corticosteroids or other immune-modulating drugs at the time of their examination. Combined, this results in a higher rate of false positive FDG findings and also in some cases a lower sensitivity to detect active disease. In this review, we therefore discuss the limitations and pitfalls of FDG PET/CT to diagnose infections and inflammation taking these issues into consideration. Our review encompasses the most commonly encountered inflammatory and infectious diseases in head and neck, in the cardiovascular system, in the abdominal organs and in the musculoskeletal system. Finally, new developments in the field of PET/CT that may help overcome some of these limitations are briefly highlighted., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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21. Toward Reliable Uptake Metrics in Large Vessel Vasculitis Studies.
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van Praagh GD, Nienhuis PH, de Jong DM, Reijrink M, van der Geest KSM, Brouwer E, Glaudemans AWJM, Sinha B, Willemsen ATM, and Slart RHJA
- Abstract
The aim of this study is to investigate the influence of sex, age, fat mass, fasting blood glucose level (FBGL), and estimated glomerular filtration rate (eGFR) on blood pool activity in patients with large vessel vasculitis (LVV). Blood pool activity was measured in the superior caval vein using mean, maximum, and peak standardized uptake values corrected for body weight (SUVs) and lean body mass (SULs) in 41 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scans of LVV patients. Sex influence on the blood pool activity was assessed with t-tests, while linear correlation analyses were used for age, fat mass, FBGL, and eGFR. Significantly higher SUVs were found in women compared with men, whereas SULs were similar between sexes. In addition, higher fat mass was associated with increased SUVs (r = 0.56 to 0.65; all p < 0.001) in the blood pool, but no correlations were found between SULs and fat mass (r = -0.25 to -0.15; all p > 0.05). Lower eGFR was associated with a higher FDG blood pool activity for all uptake values. In FDG-PET/CT studies with LVV patients, we recommend using SUL over SUV, while caution is advised in interpreting SUV and SUL measures when patients have impaired kidney function.
- Published
- 2021
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22. A Review on the Value of Imaging in Differentiating between Large Vessel Vasculitis and Atherosclerosis.
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Nienhuis PH, van Praagh GD, Glaudemans AWJM, Brouwer E, and Slart RHJA
- Abstract
Imaging is becoming increasingly important for the diagnosis of large vessel vasculitis (LVV). Atherosclerosis may be difficult to distinguish from LVV on imaging as both are inflammatory conditions of the arterial wall. Differentiating atherosclerosis from LVV is important to enable optimal diagnosis, risk assessment, and tailored treatment at a patient level. This paper reviews the current evidence of ultrasound (US), 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (FDG-PET), computed tomography (CT), and magnetic resonance imaging (MRI) to distinguish LVV from atherosclerosis. In this review, we identified a total of eight studies comparing LVV patients to atherosclerosis patients using imaging-four US studies, two FDG-PET studies, and two CT studies. The included studies mostly applied different methodologies and outcome parameters to investigate vessel wall inflammation. This review reports the currently available evidence and provides recommendations on further methodological standardization methods and future directions for research.
- Published
- 2021
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23. Visual and semiquantitative assessment of cranial artery inflammation with FDG-PET/CT in giant cell arteritis.
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Nienhuis PH, Sandovici M, Glaudemans AW, Slart RH, and Brouwer E
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- Aged, Case-Control Studies, Female, Humans, Male, Maxillary Artery pathology, Middle Aged, Retrospective Studies, Sensitivity and Specificity, Temporal Arteries pathology, Vertebral Artery pathology, Giant Cell Arteritis diagnostic imaging, Maxillary Artery diagnostic imaging, Positron Emission Tomography Computed Tomography methods, Temporal Arteries diagnostic imaging, Vertebral Artery diagnostic imaging
- Abstract
Background and Aim: Assessing cranial artery inflammation plays an important role in the diagnosis of cranial giant cell arteritis (C-GCA). However, current diagnostic tests are limited. The use of fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT imaging is an established tool for assessing large vessel inflammation but is currently not used for assessment of the cranial arteries. This study aimed to evaluate the accuracy of FDG-PET/CT in the diagnosis of biopsy proven C-GCA and its relation to clinical presentation., Methods: This retrospective case control study included temporal artery biopsy (TAB) positive C-GCA patients and age- and sex-matched controls. FDG-PET/CT scans were performed according to EANM/EARL guidelines, visually assessed by an experienced nuclear medicine physician, and semiquantitatively assessed using the maximum standardised uptake value (SUVmax). The visual and semiquantitative assessments were performed on the temporal arteries, maxillary arteries, vertebral arteries, and occipital arteries. Clinical signs and symptoms were scored for comparison., Results: A total of 24 C-GCA patients and 24 controls were included in the study. Visual analysis revealed an 83% sensitivity and a 75% specificity. Receiver operating characteristic (ROC) analysis of the semiquantitative assessment revealed a 79% sensitivity and a 92% specificity when measuring SUVmax in the cranial arteries. Visual and semiquantitative assessments showed moderate agreement (Fleiss kappa 0.55). There was a positive correlation between the number of cranial symptoms and the SUVmax in the vertebral artery., Conclusion: FDG-PET/CT can reliably diagnose C-GCA by assessing cranial artery inflammation using SUVmax. Extending the use of FDG-PET/CT to include assessment of the cranial arteries may improve its diagnostic value in GCA and provide a suitable alternative to TAB. Moderate agreement between visual and semiquantitative assessment methods suggest diagnostic accuracy may be improved by further standardisation., Competing Interests: Declaration of competing interest Dr. E. Brouwer, as an employee of the UMCG, received speaker fees and consulting fees from Roche in 2017 and 2018, which were paid to the UMCG. The other authors declare no conflicts of interest., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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24. Exploring field vegetation reflectance as an indicator of soil contamination in river floodplains.
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Kooistra L, Salas EA, Clevers JG, Wehrens R, Leuven RS, Nienhuis PH, and Buydens LM
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- Geologic Sediments chemistry, Linear Models, Metals, Heavy pharmacology, Principal Component Analysis, Radiometry methods, Rivers, Scattering, Radiation, Soil Pollutants pharmacology, Spectrum Analysis methods, Water Pollutants, Chemical, Environmental Monitoring methods, Metals, Heavy analysis, Plants drug effects, Soil Pollutants analysis
- Abstract
This study investigated the relation between vegetation reflectance and elevated concentrations of the metals Ni, Cd, Cu, Zn and Pb in river floodplain soils. High-resolution vegetation reflectance spectra in the visible to near-infrared (400-1350 nm) were obtained using a field radiometer. The relations were evaluated using simple linear regression in combination with two spectral vegetation indices: the Difference Vegetation Index (DVI) and the Red-Edge Position (REP). In addition, a multivariate regression approach using partial least squares (PLS) regression was adopted. The three methods achieved comparable results. The best R(2) values for the relation between metals concentrations and vegetation reflectance were obtained for grass vegetation and ranged from 0.50 to 0.73. Herbaceous species displayed a larger deviation from the established relationships, resulting in lower R(2) values and larger cross-validation errors. The results corroborate the potential of hyperspectral remote sensing to contribute to the survey of elevated metal concentrations in floodplain soils under grassland using the spectral response of the vegetation as an indicator. Additional constraints will, however, have to be taken into account, as results are resolution- and location-dependent.
- Published
- 2004
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25. A procedure for incorporating spatial variability in ecological risk assessment of Dutch river floodplains.
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Kooistra L, Leuven RS, Nienhuis PH, Wehrens R, and Buydens LM
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- Animals, Conservation of Natural Resources, Disasters, Ecosystem, Metals, Heavy adverse effects, Metals, Heavy pharmacokinetics, Risk Assessment, Water Movements, Environmental Monitoring methods, Food Chain, Metals, Heavy analysis, Soil Pollutants analysis, Water Pollutants analysis, Water Pollution prevention & control
- Abstract
Floodplain soils along the river Rhine in the Netherlands show a large spatial variability in pollutant concentrations. For an accurate ecological risk characterization of the river floodplains, this heterogeneity has to be included into the ecological risk assessment. In this paper a procedure is presented that incorporates spatial components of exposure into the risk assessment by linking geographical information systems (GIS) with models that estimate exposure for the most sensitive species of a floodplain. The procedure uses readily available site-specific data and is applicable to a wide range of locations and floodplain management scenarios. The procedure is applied to estimate exposure risks to metals for a typical foodweb in the Afferdensche and Deestsche Waarden floodplain along the river Waal, the main branch of the Rhine in the Netherands. Spatial variability of pollutants is quantified by overlaying appropriate topographic and soil maps resulting in the definition of homogeneous pollution units. Next to that, GIS is used to include foraging behavior of the exposed terrestrial organisms. Risk estimates from a probabilistic exposure model were used to construct site-specific risk maps for the floodplain. Based on these maps, recommendations for future management of the floodplain can be made that aim at both ecological rehabilitation and an optimal flood defense.
- Published
- 2001
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26. [Allergic contact eczema caused by Sargassum muticum in professional fishermen on Lake Grevelingen].
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van der Willigen AH, Habets JM, van Joost T, Nienhuis PH, and Stolz E
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- Humans, Male, Middle Aged, Netherlands, Dermatitis, Contact etiology, Dermatitis, Occupational etiology, Eukaryota, Fisheries, Phaeophyceae
- Published
- 1988
27. Contact allergy to iodine in Japanese sargassum.
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van der Willigen AH, Habets JM, van Joost T, Stolz E, and Nienhuis PH
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- Dermatitis, Contact diagnosis, Dermatitis, Occupational diagnosis, Humans, Iodine adverse effects, Male, Middle Aged, Patch Tests, Dermatitis, Contact etiology, Dermatitis, Occupational etiology, Eukaryota immunology, Iodine immunology, Phaeophyceae immunology
- Published
- 1988
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