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1.
Radiologe ; 60(Suppl 1): 41-53, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32430576

ABSTRACT

Imaging modalities have developed rapidly in recent decades. In addition to improved resolution as well as whole-body and faster image acquisition, the possibilities of functional and molecular examination of tissue pathophysiology have had a decisive influence on imaging diagnostics and provided ground-breaking knowledge. Many promising approaches are currently being pursued to increase the application area of devices and contrast media and to improve their sensitivity and quantitative informative value. These are complemented by new methods of data processing, multiparametric data analysis, and integrated diagnostics. The aim of this article is to provide an overview of technological innovations that will enrich clinical imaging in the future, and to highlight the resultant diagnostic options. These relate to the established imaging methods such as CT, MRI, ultrasound, PET, and SPECT but also to new methods such as magnetic particle imaging (MPI), optical imaging, and photoacoustics. In addition, approaches to radiomic image evaluation are explained and the chances and difficulties for their broad clinical introduction are discussed. The potential of imaging to describe pathophysiological relationships in ever increasing detail, both at whole-body and tissue level, can in future be used to better understand the mechanistic effect of drugs, to preselect patients to therapies, and to improve monitoring of therapy success. Consequently, the use of interdisciplinary integrated diagnostics will greatly change and enrich the profession of radiologists.


Subject(s)
Radiology , Humans , Radiology/methods
2.
Breast ; 50: 11-18, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31958661

ABSTRACT

BACKGROUND: Patients with breast cancer (BC) show strong interest in complementary and alternative medicine (CAM), particularly for adverse effects of adjuvant endocrine treatment - e.g., with letrozole. Letrozole often induces myalgia/limb pain and arthralgia, with potential noncompliance and treatment termination. This analysis investigated whether CAM before aromatase inhibitor (AI) therapy is associated with pain development and the intensity of AI-induced musculoskeletal syndrome (AIMSS) during the first year of treatment. PATIENTS AND METHODS: The multicenter phase IV PreFace study evaluated letrozole therapy in postmenopausal, hormone receptor-positive patients with early BC. Patients were asked about CAM use before, 6 months after, and 12 months after treatment started. They recorded pain every month for 1 year in a diary including questions about pain and numeric pain rating scales. Data were analyzed for patients who provided pain information for all time points. RESULTS: Of 1396 patients included, 901 (64.5%) had used CAM before AI treatment. Throughout the observation period, patients with CAM before AI treatment had higher pain values, for both myalgia/limb pain and arthralgia, than non-users. Pain increased significantly in both groups over time, with the largest increase during the first 6 months. No significant difference of pain increase was noted regarding CAM use. CONCLUSIONS: CAM use does not prevent or improve the development of AIMSS. Pain intensity was generally greater in the CAM group. Therefore, because of the risk of non-compliance and treatment discontinuation due to the development of higher pain levels, special attention must be paid to patient education and aftercare in these patients.


Subject(s)
Aromatase Inhibitors/adverse effects , Breast Neoplasms/drug therapy , Complementary Therapies , Letrozole/adverse effects , Musculoskeletal Pain/chemically induced , Aged , Arthralgia/chemically induced , Female , Germany/epidemiology , Humans , Middle Aged , Myalgia/chemically induced , Postmenopause
3.
Br J Anaesth ; 121(4): 749-757, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30236237

ABSTRACT

BACKGROUND: We evaluated the incidence of hypersensitivity or anaphylaxis after repeated single-dose sugammadex administration in non-anaesthetised adults. METHODS: In this multicentre, double-blind study (NCT02028065), healthy volunteer subjects were randomised (2:2:1 ratio) to one of three groups to receive three repeated intravenous injections of sugammadex 4 or 16 mg kg-1, or placebo, separated by a ∼5 week intervals. Targeted hypersensitivity assessments were performed 0.5, 4, and 24 h post-dosing, and hypersensitivity signs/symptoms were referred to a blinded independent Adjudication Committee. Anaphylaxis was determined per Sampson (Criterion 1). The primary endpoint was the proportion with confirmed hypersensitivity. RESULTS: Of 375 evaluable subjects, 25 had confirmed hypersensitivity [sugammadex 4 mg kg-1: 10/151 (6.6%); sugammadex 16 mg kg-1: 14/148 (9.5%); placebo: 1/76 (1.3%)]. The differences in incidence rates vs placebo were 5.3% (95% confidence interval: -0.9, 10.7) for sugammadex 4 mg kg-1 and 8.1% (1.7, 14.2) for 16 mg kg-1. Incidence was similar across sugammadex doses and dosing occasions, including in subjects with reactions to previous doses. Three subjects (16 mg kg-1 group) required antihistamines/corticosteroids and discontinued the study, per protocol; symptoms resolved and no subject required epinephrine. One subject with anaphylaxis after the first 16 mg kg-1 dose recovered completely post-treatment. There were no clinically relevant anti-sugammadex antibody or tryptase findings. CONCLUSIONS: Hypersensitivity in response to sugammadex administration can occur in healthy subjects without history of previous sugammadex exposure. Hypersensitivity incidence was similar across sugammadex doses and numerically higher than placebo, with no evidence of sensitisation with repeated administration. Hypersensitivity is unlikely to be mediated through sugammadex-specific immunoglobulin G- or E-mediated mast cell stimulation in healthy volunteers. CLINICAL TRIAL REGISTRATION: NCT02028065.


Subject(s)
Drug Hypersensitivity/epidemiology , Sugammadex/adverse effects , Adrenal Cortex Hormones/therapeutic use , Adult , Anaphylaxis/epidemiology , Anaphylaxis/etiology , Antibodies/analysis , Double-Blind Method , Drug Hypersensitivity/drug therapy , Female , Healthy Volunteers , Histamine Antagonists/therapeutic use , Humans , Immunoglobulin E/analysis , Immunoglobulin G/analysis , Incidence , Injections, Intravenous , Male , Middle Aged , Tryptases/blood , Young Adult
4.
J Neurol Sci ; 385: 225-231, 2018 02 15.
Article in English | MEDLINE | ID: mdl-29277430

ABSTRACT

PURPOSE: This study aimed to develop a conceptual understanding of the specific characteristics of palliative care in neurology and the challenges of providing palliative care in the setting of neurological illness. METHOD: The study was conducted at London Health Sciences Centre in Canada using grounded theory methodology. Qualitative thematic analysis was applied to focus group (health care providers physicians, nursing, allied health, trainees) and semi-structured interview (patient-caregiver dyads) data to explore challenges facing the delivery of palliative care in neurology. RESULTS: Specific characteristics of neurological disease that affect palliative care in neurology were identified: 1) timelines of disease progression, 2) barriers to communication arising from neurologic disease, 3) variability across disease progression, and 4) threat to personhood arising from functional and cognitive impairments related to neurologic disease. Moreover, three key challenges that shaped and complicated palliative care in neurology were identified: 1) uncertainty with respect to prognosis, support availability and disease trajectory, 2) inconsistency in information, attitudes and skills among care providers, care teams, caregivers and families, and 3) existential distress specific to neurological disease, including emotional, psychological and spiritual distress resulting from loss of function, autonomy and death. These challenges were experienced across groups, but manifested themselves in different ways for each group. CONCLUSIONS: Further research regarding prognosis, improved identification of patients with palliative care needs, developing an approach to palliative care delivery within neurology and the creation of more robust educational resources for teaching palliative neurology are expected to improve neurologists' comfort with palliative care, thereby enhancing care delivery in neurology.


Subject(s)
Caregivers/psychology , Nervous System Diseases/therapy , Neurologists/psychology , Neurology/education , Neurology/methods , Palliative Care/methods , Canada , Delivery of Health Care , Female , Humans , Male , Nervous System Diseases/psychology , Retrospective Studies
5.
Adv Health Sci Educ Theory Pract ; 22(5): 1085-1099, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28116565

ABSTRACT

Effective healthcare requires both competent individuals and competent teams. With this recognition, health professions education is grappling with how to factor team competence into training and assessment strategies. These efforts are impeded, however, by the absence of a sophisticated understanding of the the relationship between competent individuals and competent teams . Using data from a constructivist grounded theory study of team-based healthcare for patients with advanced heart failure, this paper explores the relationship between individual team members' perceived goals, understandings, values and routines and the collective competence of the team. Individual interviews with index patients and their healthcare team members formed Team Sampling Units (TSUs). Thirty-seven TSUs consisting of 183 interviews were iteratively analysed for patterns of convergence and divergence in an inductive process informed by complex adaptive systems theory. Convergence and divergence were identifiable on all teams, regularly co-occurred on the same team, and involved recurring themes. Convergence and divergence had nonlinear relationships to the team's collective functioning. Convergence could foster either shared action or collective paralysis; divergence could foster problematic incoherence or productive disruption. These findings advance our understanding of the complex relationship between the individual and the collective on a healthcare team, and they challenge conventional narratives of healthcare teamwork which derive largely from acute care settings and emphasize the importance of common goals and shared mental models. Complex adaptive systems theory helps us to understand the implications of these insights for healthcare teams' delivery of care for the complex, chronically ill.


Subject(s)
Patient Care Team , Cooperative Behavior , Grounded Theory , Group Processes , Heart Failure/therapy , Humans , Interpersonal Relations , Interviews as Topic , Patient Care Team/organization & administration , Qualitative Research
7.
Phys Med Biol ; 61(9): 3500-26, 2016 May 07.
Article in English | MEDLINE | ID: mdl-27049898

ABSTRACT

The combination of positron emission tomography (PET) and magnetic resonance imaging (MRI) as a multi-modal imaging technique is considered very promising and powerful with regard to in vivo disease progression examination, therapy response monitoring and drug development. However, PET-MRI system design enabling simultaneous operation with unaffected intrinsic performance of both modalities is challenging. As one of the major issues, both the PET detectors and the MRI radio-frequency (RF) subsystem are exposed to electromagnetic (EM) interference, which may lead to PET and MRI signal-to-noise ratio (SNR) deteriorations. Early digitization of electronic PET signals within the MRI bore helps to preserve PET SNR, but occurs at the expense of increased amount of PET electronics inside the MRI and associated RF field emissions. This raises the likelihood of PET-related MRI interference by coupling into the MRI RF coil unwanted spurious signals considered as RF noise, as it degrades MRI SNR and results in MR image artefacts. RF shielding of PET detectors is a commonly used technique to reduce PET-related RF interferences, but can introduce eddy-current-related MRI disturbances and hinder the highest system integration. In this paper, we present RF interference reduction methods which rely on EM field coupling-decoupling principles of RF receive coils rather than suppressing emitted fields. By modifying clock frequencies and changing clock phase relations of digital circuits, the resulting RF field emission is optimised with regard to a lower field coupling into the MRI RF coil, thereby increasing the RF silence of PET detectors. Our methods are demonstrated by performing FPGA-based clock frequency and phase shifting of digital silicon photo-multipliers (dSiPMs) used in the PET modules of our MR-compatible Hyperion II (D) PET insert. We present simulations and magnetic-field map scans visualising the impact of altered clock phase pattern on the spatial RF field distribution, followed by MRI noise and SNR scans performed with an operating PET module using different clock frequencies and phase patterns. The methods were implemented via firmware design changes without any hardware modifications. This introduces new means of flexibility by enabling adaptive RF interference reduction optimisations in the field, e.g. when using a PET insert with different MRI systems or when different MRI RF coil types are to be operated with the same PET detector.


Subject(s)
Electromagnetic Fields , Image Processing, Computer-Assisted/instrumentation , Magnetic Resonance Imaging/methods , Phantoms, Imaging , Positron-Emission Tomography/methods , Signal-To-Noise Ratio , Artifacts , Humans , Radio Waves
8.
Phys Med Biol ; 60(6): 2231-55, 2015 Mar 21.
Article in English | MEDLINE | ID: mdl-25684065

ABSTRACT

PET (positron emission tomography) with its high sensitivity in combination with MRI (magnetic resonance imaging) providing anatomic information with good soft-tissue contrast is considered to be a promising hybrid imaging modality. However, the integration of a PET detector into an MRI system is a challenging task since the MRI system is a sensitive device for external disturbances and provides a harsh environment for electronic devices. Consequently, the PET detector has to be transparent for the MRI system and insensitive to electromagnetic disturbances. Due to the variety of MRI protocols imposing a wide range of requirements regarding the MR-compatibility, an extensive study is mandatory to reliably assess worst-case interference phenomena between the PET detector and the MRI scanner. We have built the first preclinical PET insert, designed for a clinical 3 T MRI, using digital silicon photomultipliers (digital SiPM, type DPC 3200-22, Philips Digital Photon Counting). Since no thorough interference investigation with this new digital sensor has been reported so far, we present in this work such a comprehensive MR-compatibility study. Acceptable distortion of the B0 field homogeneity (volume RMS = 0.08 ppm, peak-to-peak value = 0.71 ppm) has been found for the PET detector installed. The signal-to-noise ratio degradation stays between 2-15% for activities up to 21 MBq. Ghosting artifacts were only found for demanding EPI (echo planar imaging) sequences with read-out gradients in Z direction caused by additional eddy currents originated from the PET detector. On the PET side, interference mainly between the gradient system and the PET detector occurred: extreme gradient tests were executed using synthetic sequences with triangular pulse shape and maximum slew rate. Under this condition, a relative degradation of the energy (⩽10%) and timing (⩽15%) resolution was noticed. However, barely measurable performance deterioration occurred when morphological MRI protocols are conducted certifying that the overall PET performance parameters remain unharmed.


Subject(s)
Amplifiers, Electronic , Magnetic Resonance Imaging/methods , Multimodal Imaging/methods , Photons , Positron-Emission Tomography/methods , Artifacts , Magnetic Resonance Imaging/instrumentation , Multimodal Imaging/instrumentation , Positron-Emission Tomography/instrumentation , Signal-To-Noise Ratio , Silicon
10.
J Perinatol ; 33(9): 740-2, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23986093

ABSTRACT

The epidemiology, etiology and outcome of neonatal sepsis are changing over time. While monitoring longitudinal trends in neonatal sepsis in our institution, we encountered a case of late-onset neonatal sepsis due to Leclercia adecarboxylata. A Gram-negative rod previously not encountered in the clinical setting, L. adecarboxylata has recently emerged as a human pathogen, primarily in immunosuppressed patients. This report describes the clinical and laboratory features of this case of late-onset L. adecarboxylata sepsis, and reviews significant features of infection associated with this emerging pathogen.


Subject(s)
Enterobacteriaceae Infections/diagnosis , Enterobacteriaceae , Multiple Organ Failure/etiology , Respiratory Distress Syndrome, Newborn/therapy , Shock, Septic/diagnosis , Stomach Rupture/complications , Enterobacteriaceae Infections/therapy , Fatal Outcome , Female , Humans , Infant, Newborn , Infant, Premature , Multiple Organ Failure/diagnosis , Multiple Organ Failure/therapy , Respiratory Distress Syndrome, Newborn/complications , Shock, Septic/therapy , Stomach Rupture/diagnosis , Stomach Rupture/therapy
11.
Vet Q ; 33(2): 94-107, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23745732

ABSTRACT

The immune system is important for protection against pathogens and malignant cells. However, malfunction of the immune system can also result in detrimental auto-immune diseases, inflammatory diseases, cancers and allergies. The aryl hydrocarbon receptor (AhR), present in numerous tissues and cell subsets, including cells of the immune system, plays an important role in the functioning of the immune system. Activation of the AhR is for example associated with various effects on dendritic cells (DCs), regulatory T cells and the Th1/Th2 cell balance. These cells play a major role in the development of food allergy. Food allergy is an increasing health problem in both humans and animals. Despite the knowledge in risk factors and cellular mechanisms for food allergy, no approved treatments are available yet. Recently, it has been shown that activation of the AhR by dioxin-like compounds suppresses allergic sensitization by suppressing the absolute number of precursor and effector T cells, by preserving CD4(+)CD25(+)Foxp3(+) Treg cells and by affecting DCs and their interaction with effector T cells. Future research should elucidate whether and how AhR activation can be used to interfere in food allergic responses in humans and in animals. This may lead to new prevention strategies and therapeutic possibilities for food allergy.


Subject(s)
Food Hypersensitivity/immunology , Food Hypersensitivity/veterinary , Immune System/drug effects , Receptors, Aryl Hydrocarbon/immunology , Allergens/immunology , Animals , Dioxins/toxicity , Environmental Pollutants/toxicity , Humans
12.
Immunobiology ; 218(8): 1055-62, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23433705

ABSTRACT

Aryl hydrocarbon receptor (AhR) activation by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) suppresses peanut sensitization by affecting T cell subsets. However, effects of AhR activation on dendritic cells (DC) in an allergic setting were not investigated yet. Therefore, we analysed the effects of AhR activation on DC phenotype in vivo, as well as their ex vivo potency to stimulate allergen-specific splenic T cells and to induce CD4+CD25+Foxp3+ regulatory (T(reg)) cells. C3H/HeOuJ mice were treated with TCDD by gavage and subsequently sensitized to peanut extract (PE). After eight days, mice were sacrificed and DC in spleen and mesenteric lymph nodes (MLN) were characterized or cocultured with PE-specific CD4+ T cells. AhR activation almost doubled the absolute number of CD11c+CD103+ DC, while not affecting CD11b+ DC, the absolute number of DC, the expression of the activation makers MHCII, CD86, CD80, CD40, CD54 and CD8 on CD11c+ and the activation status of CD11c+CD103+ DC in the spleen. In the MLN, TCDD decreased the absolute number of DC and CD103+ DC, while not affecting CD11b+ DC and the expression of activation markers on DC. PE-pulsed splenic DC from TCDD-treated mice suppressed IL-5, IL-13 and IFN-γ production by PE-specific T cells, but did not induce CD4+CD25+Foxp3+ T(reg) cells. This suppression of cytokine production was not mediated by the TCDD-induced increase in CD103+ DC in the spleen. Combined, these results indicate that AhR activation suppresses the initiation of food allergic responses by affecting DC and their interaction with effector T cells.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , Dendritic Cells/immunology , Immunization , Peanut Hypersensitivity/immunology , Receptors, Aryl Hydrocarbon/metabolism , Animals , Arachis/immunology , Biomarkers/metabolism , Female , Forkhead Transcription Factors/metabolism , Hypersensitivity/immunology , Interleukin-2 Receptor alpha Subunit/metabolism , Lymph Nodes/cytology , Lymph Nodes/immunology , Lymphocyte Activation/drug effects , Lymphocyte Activation/immunology , Mice , Mice, Inbred C3H , Polychlorinated Dibenzodioxins , Spleen/cytology , Spleen/immunology
13.
Toxicol Lett ; 215(2): 100-9, 2012 Nov 30.
Article in English | MEDLINE | ID: mdl-23041608

ABSTRACT

Aryl hydrocarbon receptor (AhR) activation suppresses immune responses, including allergic sensitization, by increasing the percentage of regulatory (Treg) cells. Furthermore, AhR activation is known to affect thymic precursor T cells. However, the effect of AhR activation on intrathymic CD4+CD25+Foxp3+ Treg cells is unknown. Therefore, we investigated the effect of AhR activation on the percentage and number of CD4+CD25+Foxp3+ Treg cells during allergic sensitization in relevant immunological organs. C3H/HeOuJ mice were treated on day 0 with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and subsequently sensitized to peanut. On day 8, mice were sacrificed and thymus, spleen and mesenteric lymph nodes (MLN) were isolated. TCDD treatment decreased the number of CD4-CD8-, CD4+CD8+, CD4+CD8- and CD4-CD8+ precursor T cells, but not the number of thymic CD4+CD25+Foxp3+ Treg cells. TCDD treatment increased the number of splenic CD4+CD25+Foxp3+ Treg cells and decreased Th1, Th2 and cytotoxic T cells in the spleen. This appeared to be independent of allergic sensitization. In MLN, TCDD treatment suppressed the increase of the number of CD4+CD25+Foxp3+ Treg cells, Th1, Th2 and cytotoxic T cells induced by peanut sensitization. Together, TCDD treatment preserves thymic CD4+CD25+Foxp3+ Treg cells and decreases peripheral T helper and cytotoxic T cells. This effect of TCDD may contribute to the increased influence of CD4+CD25+Foxp3+ Treg cells on immune mediated responses and to the understanding of how AhR activation modulates immune mediated diseases, including food allergy.


Subject(s)
Lymphoid Tissue/immunology , Peanut Hypersensitivity/immunology , Polychlorinated Dibenzodioxins/toxicity , Receptors, Aryl Hydrocarbon/immunology , T-Lymphocyte Subsets/immunology , T-Lymphocytes, Regulatory/immunology , Animals , Female , Flow Cytometry , Lymphoid Tissue/cytology , Lymphoid Tissue/drug effects , Mice , Mice, Inbred C3H , T-Lymphocyte Subsets/cytology , T-Lymphocyte Subsets/drug effects , T-Lymphocytes, Cytotoxic/drug effects , T-Lymphocytes, Cytotoxic/immunology , T-Lymphocytes, Regulatory/cytology , T-Lymphocytes, Regulatory/drug effects , Th1 Cells/drug effects , Th1 Cells/immunology , Th2 Cells/drug effects , Th2 Cells/immunology
14.
Phys Med Biol ; 56(20): 6597-613, 2011 Oct 21.
Article in English | MEDLINE | ID: mdl-21937775

ABSTRACT

We have implemented and evaluated a framework for simulating simultaneous dynamic PET-MR data using the anatomic and dynamic information from real MR acquisitions. PET radiotracer distribution is simulated by assigning typical FDG uptake values to segmented MR images with manually inserted additional virtual lesions. PET projection data and images are simulated using analytic forward projections (including attenuation and Poisson statistics) implemented within the image reconstruction package STIR. PET image reconstructions are also performed with STIR. The simulation is validated with numerical simulation based on Monte Carlo (GATE) which uses more accurate physical modelling, but has 150× slower computation time compared to the analytic method for ten respiratory positions and is 7000× slower when performing multiple realizations. Results are validated in terms of region of interest mean values and coefficients of variation for 65 million coincidences including scattered events. Although some discrepancy is observed, agreement between the two different simulation methods is good given the statistical noise in the data. In particular, the percentage difference of the mean values is 3.1% for tissue, 17% for the lungs and 18% for a small lesion. The utility of the procedure is demonstrated by simulating realistic PET-MR datasets from multiple volunteers with different breathing patterns. The usefulness of the toolkit will be shown for performance investigations of the reconstruction, motion correction and attenuation correction algorithms for dynamic PET-MR data.


Subject(s)
Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Positron-Emission Tomography/methods , Databases, Factual , Female , Humans , Male , Models, Theoretical , Monte Carlo Method , Movement , Phantoms, Imaging , Respiration , Time Factors
15.
Med Phys ; 38(7): 3995-4000, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21858996

ABSTRACT

PURPOSE: Integration of positron emission tomography (PET) and magnetic resonance (MR) in a merged device requires shielding of the PET detector electronics. The authors demonstrate that a multiple shell setup exhibits advantages over a single shell shielding enclosure. METHODS: A spherical shell model is used to derive analytical results. Numerical computations of the electromagnetic fields with a commercial software package (FEKO) and experiments are used to confirm our findings. RESULTS: Replacing a single shell enclosure by a multilayer approach barely changes its behavior toward low frequency magnetic fields (MR gradient fields), while improving shielding at high frequencies (proton resonant frequency) by orders of magnitude. CONCLUSIONS: For a given required shielding factor at the proton resonant frequency, the eddy currents induced by the MR gradient fields may be reduced by employing a multiple shell setup.


Subject(s)
Image Enhancement/instrumentation , Magnetic Resonance Imaging/instrumentation , Positron-Emission Tomography/instrumentation , Radiation Protection/instrumentation , Subtraction Technique/instrumentation , Equipment Design , Equipment Failure Analysis , Humans , Phantoms, Imaging , Reproducibility of Results , Sensitivity and Specificity
16.
Toxicol Sci ; 123(2): 491-500, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21804081

ABSTRACT

Food allergy is an increasing health problem in Western countries. Previously, it has been shown that the intensity of food allergic reactions can be regulated by regulatory T (T(reg)) cells. In addition, it has been shown that activation of the aryl hydrocarbon receptor (AhR) regulates T-cell responses by induction of T(reg) cells. Therefore, we hypothesized that activation of the AhR pathway can suppress development of food allergic responses through the induction of T(reg) cells. This was investigated by using a mouse model for peanut allergy. C3H/HeOuJ mice (AhR(b)(-2)) were sensitized to peanut by administering peanut extract (PE) by gavage in the presence of cholera toxin and were treated with the prototypical AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (0.6, 1.7, 5, and 15 µg/kg body weight) on days 3 and 11 orally. The functional role of CD4(+)CD25(+)Foxp3(+) T(reg) cells was investigated by depleting these cells with anti-CD25 mAb during sensitization to PE. TCDD treatment dose dependently suppressed sensitization to peanut (PE-specific IgE, IgG1, and IgG2a and PE-induced IL-5, IL-10, and IL-13, respectively). The percentage, but not the number, of CD4(+)CD25(+)Foxp3(+) T(reg) cells dose dependently increased by AhR activation in both spleen and mesenteric lymph nodes. Depletion of CD4(+)CD25(+)Foxp3(+) T(reg) cells markedly reversed the suppressive effect of TCDD on PE-specific antibody levels and PE-induced IL-5, IL-10, and IL-13 cytokine production. Present data demonstrate for the first time that activation of the AhR by TCDD suppressed the development of Th2-mediated food allergic responses. A functional shift within the CD4(+) cell population toward CD4(+)CD25(+)Foxp3(+) T(reg) cells appeared to underlie this effect. This suggests that the AhR pathway might provide potential therapeutic targets to treat food allergic diseases.


Subject(s)
Allergens/immunology , Arachis/immunology , Immune Tolerance/immunology , Peanut Hypersensitivity/immunology , Receptors, Aryl Hydrocarbon/biosynthesis , Animals , Antibodies, Blocking/pharmacology , Arachis/chemistry , Disease Models, Animal , Dose-Response Relationship, Drug , Drug Antagonism , Forkhead Transcription Factors/metabolism , Mice , Mice, Inbred C3H , Microsomes, Liver/drug effects , Microsomes, Liver/metabolism , Peanut Hypersensitivity/metabolism , Plant Extracts/immunology , Plant Extracts/toxicity , Polychlorinated Dibenzodioxins/pharmacology , T-Lymphocytes, Regulatory/immunology
17.
Eur J Nucl Med Mol Imaging ; 38(1): 138-52, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20922522

ABSTRACT

PURPOSE: The combination of positron emission tomography (PET) and magnetic resonance (MR) tomography in a single device is anticipated to be the next step following PET/CT for future molecular imaging application. Compared to CT, the main advantages of MR are versatile soft tissue contrast and its capability to acquire functional information without ionizing radiation. However, MR is not capable of measuring a physical quantity that would allow a direct derivation of the attenuation values for high-energy photons. METHODS: To overcome this problem, we propose a fully automated approach that uses a dedicated T1-weighted MR sequence in combination with a customized image processing technique to derive attenuation maps for whole-body PET. The algorithm automatically identifies the outer contour of the body and the lungs using region-growing techniques in combination with an intensity analysis for automatic threshold estimation. No user interaction is required to generate the attenuation map. RESULTS: The accuracy of the proposed MR-based attenuation correction (AC) approach was evaluated in a clinical study using whole-body PET/CT and MR images of the same patients (n = 15). The segmentation of the body and lung contour (L-R directions) was evaluated via a four-point scale in comparison to the original MR image (mean values >3.8). PET images were reconstructed using elastically registered MR-based and CT-based (segmented and non-segmented) attenuation maps. The MR-based AC showed similar behaviour as CT-based AC and similar accuracy as offered by segmented CT-based AC. Standardized uptake value (SUV) comparisons with reference to CT-based AC using predefined attenuation coefficients showed the largest difference for bone lesions (mean value ± standard variation of SUV(max): -3.0% ± 3.9% for MR; -6.5% ± 4.1% for segmented CT). A blind comparison of PET images corrected with segmented MR-based, CT-based and segmented CT-based AC afforded identical lesion detectability, but slight differences in image quality were found. CONCLUSION: Our MR-based attenuation correction method offers similar correction accuracy as offered by segmented CT. According to the specialists involved in the blind study, these differences do not affect the diagnostic value of the PET images.


Subject(s)
Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Positron-Emission Tomography/methods , Whole Body Imaging/methods , Adult , Aged , Automation , Female , Humans , Male , Middle Aged , Tomography, X-Ray Computed
18.
Palliat Med ; 23(3): 266-73, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19318462

ABSTRACT

Malignant wounds, caused by the direct invasion of cancer into the skin, occur in cancer patients with primary skin tumours and as cutaneous metastasis in approximately 10% of patients with metastatic internal malignancies. Malignant wounds have a profound impact on patients, family members and health care providers. The assessment of the patient with malignant wounds can be complex and there is no widely accepted, consistent approach. Valid, descriptive survey research methods were used to develop the Malignant Wound Assessment Tool (MWAT). The authors developed two versions of the MWAT: a brief clinical version (MWAT-C) and a more detailed research version (MWAT-R). Domains include clinical wound features, physical effects and emotional and social impacts of the wound. The two tools underwent content and construct validity testing using a Delphi process. An international panel of professionals with clinical or research expertise related to malignant wounds was formed. Panelists participated in two rounds of review for each tool. Development and face validity testing of the MWAT-C and MWAT-R tools through the Delphi process have resulted in tools ready for clinical application and will support clinical and research activities to improve care for patients with this devastating condition.


Subject(s)
Delphi Technique , Palliative Care , Research Design , Skin Neoplasms/pathology , Wounds and Injuries/pathology , Humans , Skin Neoplasms/classification , Skin Neoplasms/secondary , Surveys and Questionnaires/standards , Wounds and Injuries/classification
19.
Clin Exp Immunol ; 150(2): 263-73, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17892510

ABSTRACT

In vitro studies have contributed substantially to the understanding of immunopathology of respiratory syncytial virus (RSV)-mediated disease. In the present study we compared the effect of RSV-infected dendritic cells on the time-course of the primary and memory/effector T cell response in vitro. Cultures with uninfected dendritic cells known to elicit T helper 2 (Th2) responses and with polyinosinic-polycytidylic acid (poly-IC)-stimulated dendritic cells known to elicit Th1 responses served as controls. At day 1 after stimulation there was a high proportion of interleukin (IL)-2 and tumour necrosis factor (TNF)-alpha-producing T cells with no difference in number of producing T cells as well as concentration of secreted cytokines between RSV-infected and control cultures. However, up to day 3 generation of IFN-gamma was reduced markedly. In addition, there was a reduced proliferation in RSV cultures. At day 7 the RSV-treated cultures showed a preponderance of IL-4 generation. At days 21-24, after three rounds of restimulation, memory/effector T cells matured under the influence of RSV were still not fully polarized but in contrast to the primary response displayed a predominance of Th1 cytokines. Contact with RSV-infected HEp-2 cells inhibited proliferation of T cells; memory effector T cells were less sensitive to contact inhibition than naive T cells. In addition, RSV inhibited the stimulated rearrangement of cortical actin more effectively in naive compared to memory T cells. In summary, we have shown that RSV infection of dendritic cells has a distinct modulatory effect on the primary response and a less pronounced effect on the memory response.


Subject(s)
Dendritic Cells/immunology , Dendritic Cells/virology , Respiratory Syncytial Virus Infections/immunology , T-Lymphocyte Subsets/immunology , Antigen Presentation/immunology , Cell Proliferation , Cells, Cultured , Cytokines/biosynthesis , Humans , Immune Tolerance , Immunologic Memory , Immunophenotyping , Lymphocyte Activation/immunology
20.
Nuklearmedizin ; 46(1): 36-42, 2007.
Article in English | MEDLINE | ID: mdl-17299653

ABSTRACT

UNLABELLED: The AIM of this study was to determine the clinical relevance of compensating SPECT data for patient specific attenuation by the use of CT data simultaneously acquired with SPECT/CT when analyzing the skeletal uptake of polyphosphonates (DPD). Furthermore, the influence of misregistration between SPECT and CT data on uptake ratios was investigated. METHODS: Thirty-six data sets from bone SPECTs performed on a hybrid SPECT/CT system were retrospectively analyzed. Using regions of interest (ROIs), raw counts were determined in the fifth lumbar vertebral body, its facet joints, both anterior iliacal spinae, and of the whole transversal slice. ROI measurements were performed in uncorrected (NAC) and attenuation-corrected (AC) images. Furthermore, the ROI measurements were also performed in AC scans in which SPECT and CT images had been misaligned by 1 cm in one dimension beforehand (ACX, ACY, ACZ). RESULTS: After AC, DPD uptake ratios differed significantly from the NAC values in all regions studied ranging from 32% for the left facet joint to 39% for the vertebral body. AC using misaligned pairs of patient data sets led to a significant change of whole-slice uptake ratios whose differences ranged from 3,5 to 25%. For ACX, the average left-to-right ratio of the facet joints was by 8% and for the superior iliacal spines by 31% lower than the values determined for the matched images (p < 0.05). CONCLUSIONS: AC significantly affects DPD uptake ratios. Furthermore, misalignment between SPECT and CT may introduce significant errors in quantification, potentially also affecting left-to-right ratios. Therefore, at clinical evaluation of attenuation-corrected scans special attention should be given to possible misalignments between SPECT and CT.


Subject(s)
Bone and Bones/diagnostic imaging , Neoplasms/diagnostic imaging , Tomography, Emission-Computed, Single-Photon/methods , Tomography, Spiral Computed/methods , Breast Neoplasms/diagnostic imaging , Female , Humans , Image Processing, Computer-Assisted , Male , Phantoms, Imaging
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