Practice parameters for diagnosing and managing iodinated contrast media hypersensitivity.

Immediate and nonimmediate hypersensitivity reactions to iodinated contrast media (ICM) have been reported to occur in a frequency of about 0.5%-3% of patients receiving nonionic ICM. The diagnosis and management of these patients vary among guidelines published by various national and international scientific societies, with recommendations ranging from avoidance or premedication to drug provocation test. This position paper aims to give recommendations for the management of patients with ICM hypersensitivity reactions and analyze controversies in this area. Skin tests are recommended as the initial step for diagnosing patients with immediate and nonimmediate hypersensitivity reactions; besides, they may also help guide on tolerability of alternatives. Re-exposition or drug provocation test should only be done with skin test-negative ICMs. The decision for performing either re-exposition or drug provocation test needs to be taken based on a risk-benefit analysis. The role of in vitro tests for diagnosis and pretreatment for preventing reactions remains controversial.

Monitoring of tumor burden in vivo by optical imaging in a xenograft SCID mouse model: evaluation of two fluorescent proteins of the GFP-superfamily.

BACKGROUND: Mouse models of human-malignant-melanoma (MM) are important tools to study tumor dynamics. The enhanced green fluorescent protein (EGFP) is widely used in molecular imaging approaches, together with optical scanners, and fluorescence imaging. PURPOSE: Currently, there are no data available as to whether other fluorescent proteins are more suitable. The goal of this preclinical study was to analyze two fluorescent proteins of the GFP superfamily under real-time in vivo conditions using fluorescence reflectance imaging (FRI). MATERIAL AND METHODS: The human melanoma cell line MeWo was stable transfected with one plasmid: pEGFP-C1 or pDsRed1-N1. We investigated two severe combined immunodeficiency (SCID)-mice groups: A (solid xenografts) and B (xenografts as metastases). After three weeks, the animals were weekly imaged by FRI. Afterwards the mice were euthanized and metastases were imaged in situ: to quantify the cutis-dependent reduction of emitted light, we compared signal intensities obtained by metastases in vivo with signal intensities obtained by in situ liver parenchyma preparations. RESULTS: More than 90% of cells were stable transfected. EGFP-/DsRed-xenograft tumors had identical growth kinetics. In vivo the emitted light by DsRed tumors/metastases was much brighter than by EGFP. DsRed metastases were earlier (3 vs. 5 weeks) and much more sensitive detectable than EGFP metastases. Cutis-dependent reduction of emitted light was greater in EGFP than in DsRed mice (tenfold). Autofluorescence of DsRed was lower than of EGFP. CONCLUSION: We established an in vivo xenograft mouse model (DsRed-MeWo) that is reliable, reproducible, and superior to the EGFP model as a preclinical tool to study innovative therapies by FRI under real-time in vivo conditions.

Improved identification of DNA double strand breaks: γ-H2AX-epitope visualization by confocal microscopy and 3D reconstructed images.

Currently, in the context of radiology, irradiation-induced and other genotoxic effects are determined by visualizing DSB-induced DNA repair through γ-H2AX immunofluorescence and direct counting of the foci by epifluorescence microscopy. This procedure, however, neglects the 3D nature of the nucleus. The aim of our study was to use confocal microscopy and 3D reconstructed images to improve documentation and analysis of γ-H2AX fluorescence signals after diagnostic examinations. Confluent, non-dividing MRC-5 lung fibroblasts were irradiated in vitro with a Cs-137 source and exposed to radiation doses up to 1000 mGy before fixation and staining with an antibody recognizing the phosphorylated histone variant γ-H2AX. The 3D distribution of γ-H2AX foci was visualized using confocal laser scanning microscopy. 3D reconstruction of the optical slices and γ-H2AX foci counting were performed using Imaris Image Analysis software. In parallel, γ-H2AX foci were counted visually by epifluorescence microscopy. In addition, whole blood was exposed ex vivo to the radiation doses from 200 to 1600 mGy. White blood cells (WBCs) were isolated and stained for γ-H2AX. In fibroblasts, epifluorescence microscopy alone visualized the entirety of fluorescence signals as integral, without correct demarcation of single foci, and at 1000 mGy yielded on average 11.1 foci by manual counting of 2D images in comparison to 36.1 foci with confocal microscopy and 3D reconstruction (p < 0.001). The procedure can also be applied for studies on WBCs. In contrast to epifluorescence microscopy, confocal microscopy and 3D reconstruction enables an improved identification of DSB-induced γ-H2AX foci, allowing for an unbiased, ameliorated quantification.

Biological applications of magnetic nanoparticles.

In this review an overview about biological applications of magnetic colloidal nanoparticles will be given, which comprises their synthesis, characterization, and in vitro and in vivo applications. The potential future role of magnetic nanoparticles compared to other functional nanoparticles will be discussed by highlighting the possibility of integration with other nanostructures and with existing biotechnology as well as by pointing out the specific properties of magnetic colloids. Current limitations in the fabrication process and issues related with the outcome of the particles in the body will be also pointed out in order to address the remaining challenges for an extended application of magnetic nanoparticles in medicine.

Magnetic resonance cell-tracking studies: spectrophotometry-based method for the quantification of cellular iron content after loading with superparamagnetic iron oxide nanoparticles.

The purpose of this article is to present a user-friendly tool for quantifying the iron content of superparamagnetic labeled cells before cell tracking by magnetic resonance imaging (MRI). Iron quantification was evaluated by using Prussian blue staining and spectrophotometry. White blood cells were labeled with superparamagnetic iron oxide (SPIO) nanoparticles. Labeling was confirmed by light microscopy. Subsequently, the cells were embedded in a phantom and scanned on a 3 T magnetic resonance tomography (MRT) whole-body system. Mean peak wavelengths λ(peak) was determined at A(720 nm) (range 719-722 nm). Linearity was proven for the measuring range 0.5 to 10 µg Fe/mL (r  =  .9958; p  =  2.2 × 10(-12)). The limit of detection was 0.01 µg Fe/mL (0.1785 mM), and the limit of quantification was 0.04 µg Fe/mL (0.714 mM). Accuracy was demonstrated by comparison with atomic absorption spectrometry. Precision and robustness were also proven. On T(2)-weighted images, signal intensity varied according to the iron concentration of SPIO-labeled cells. Absorption spectrophotometry is both a highly sensitive and user-friendly technique that is feasible for quantifying the iron content of magnetically labeled cells. The presented data suggest that spectrophotometry is a promising tool for promoting the implementation of magnetic resonance-based cell tracking in routine clinical applications (from bench to bedside).

Induction of upregulation and downregulation of the T-cell activation marker CD98 in patients undergoing contrast-enhanced CT with iodinated non-ionic dimeric contrast medium.

OBJECTIVE: This study was designed to determine prospectively the expression of the multifunctional CD98 protein in peripheral white blood cells in patients receiving iodinated contrast media (CM) for a computed tomography (CT) examination. MATERIALS AND METHODS: In 12 adult patients that received non-ionic dimeric CM (iosimenol or iodixanol), the expression of CD98 was analyzed from samples of peripheral white blood cells obtained prior to, one hour, and 24 hours after CM injection by the use of flow cytometry analysis and the use of the direct immunofluorescence technique. RESULTS: Overall, expression of CD98 was significantly downregulated 24 hours after CM injection (51.9%+/-10.8% vs. 38.8%+/-16.9%; p < 0.04). Patients that received iosimenol exhibited a more pronounced but not significant decrease of CD98 expression both one hour and 24 hours after CM injection. In an analysis of specific patient responses, CD98 downregulation occurred in eight patients. In two patients, CD98 was upregulated, and in the remaining two patients, expression remained unchanged. No patient acquired an adverse CM reaction. CONCLUSION: This is the first demonstration that CM may be a regulator of CD98 expression. To determine if upregulation is associated with an increased risk for the acquisition of an adverse CM-induced hypersensitivity reaction and if downregulation is associated without a risk for the acquisition of an adverse CM-induced hypersensitivity reaction, further studies with a larger population of patients are required.

Enhancing patient value efficiently: Medical history interviews create patient satisfaction and contribute to an improved quality of radiologic examinations.

Diagnostic radiology examinations are generally very efficient processes optimized for high throughput and for serving the needs of physicians. On the downside, streamlined examinations disrupt the personal relationship between diagnosticians and patients. The radiology associations RSNA and ACR consider low visibility of radiologists a threat to the profession. Therefore, they launched counter-acting initiatives that aim at increasing patient satisfaction by providing more personal attention and care, and by raising knowledge about the discipline. However, they did not formulate concrete instructions on how to integrate care by radiologists into the examination process while inhibiting the flow minimally. From an internal patient satisfaction survey, we have seen that patients rated satisfaction with care and attention by physicians relatively low, indicating that patients would welcome a possibility to communicate with radiologists. In a controlled experimental setting, we have then changed our process to include a short medical history interview. Thereby we could corroborate that lack of educated communication is the primary cause of diminished satisfaction and could establish that the duration of the encounter is not critical to achieving improvement. Importantly, the interview also helped to improve the quality of the examination. Thus, short medical history interviews are a very efficient way to increase value by maximizing patient satisfaction and examination quality. Our approach is easy to implement in other radiology clinics that are interested in becoming more patient-centered and in raising patient satisfaction.

IgG deposits can be detected in cell nuclei of patients with both lupus erythematosus and malignancy.

The purpose was to find immunological disturbances in lupus erythematosus (LE) patients with concomitant malignancy. 159 LE patients have been analyzed. Routine laboratory analyses including screening of serum autoantibodies and analyzing peripheral blood mononuclear cells by using flow cytometry have been performed. Malignant diseases have been revealed in 12 (7.5%) cases. All patients suffered from internal malignancies. LE patients with vs without malignancy had significantly decreased anti-double stranded DNA (16.6 vs 31.6%; p < 0.05) and increased anti-SSA/SSB (83.3 vs 32.2%/26.4%; p < 3 x 10(-12)) antibodies. Patients with neoplastic disease had increased IgG within the cell nuclei (76.6% +/- 9.6 vs 51.8 +/- 4.6%; p < 2 x 10(-7)). IgG penetrating living cells has been shown previously in SLE but has so far not been found in association to LE patients with malignant disease.

Iodinated Contrast Media and the Alleged "Iodine Allergy": An Inexact Diagnosis Leading to Inferior Radiologic Management and Adverse Drug Reactions.

Purpose To test the hypothesis that the incomplete diagnosis "iodine allergy" is a possibly dangerous concept for patients under routine radiologic conditions. Materials and Methods 300 patients with a history of an "iodine allergy" were retrospectively screened and compared with two age-, sex-, and procedure-matched groups of patients either diagnosed with a nonspecific "iodine contrast medium (ICM) allergy" or an allergy to a specific ICM agent. For all groups, the clinical symptoms of the most recent past adverse drug reaction (ADR), prophylactic actions taken for subsequent imaging, and ultimate outcome were recorded and analyzed. Results The diagnosis "iodine allergy" was not otherwise specified in 84.3 % patients. For this group, in most cases, the symptoms of the previous ADRs were not documented. In contrast, the type of ADR was undocumented in only a minority of patients in the comparison groups. In the group of patients with an "iodine allergy" the percentage of unenhanced CT scans was greater than within the other two groups (36.7 % vs. 28.7 %/18.6 %). ADRs following prophylactic measures were only observed in the "iodine allergy" group (OR of 9.24 95 % CI 1.16 - 73.45; p < 0.04). Conclusion This data confirms the hypothesis that the diagnosis "iodine allergy" is potentially dangerous and results in uncertainty in clinical management and sometimes even ineffective prophylactic measures. Key points · The term "iodine allergy" is imprecise, because it designates allergies against different substance classes, such as disinfectants with complexed iodine and contrast media containing covalently bound iodine.. · There is a clear correlation between the exactness of the diagnosis - from the alleged "iodine allergy" to "contrast media allergy" to naming the exact culprit CM - and the quality of documentation of the symptoms.. · Management of patients diagnosed with "iodine allergy" was associated with uncertainty leading to unenhanced scans and sometimes unnecessary prophylactic actions.. · The term "iodine allergy" should be omitted, because it is potentially dangerous and can decrease the quality of radiology exams.. Citation Format · Böhm Ingrid, Nairz Knud, Morelli John N et al. Iodinated Contrast Media and the Alleged "Iodine Allergy": An Inexact Diagnosis Leading to Inferior Radiologic Management and Adverse Drug Reactions. Fortschr Röntgenstr 2017; 189: 326 - 332.

Myths and misconceptions concerning contrast media-induced anaphylaxis: a narrative review.

Contrast-enhanced radiological examinations are an increasingly important diagnostic tool in modern medicine. All approved and available contrast media (iodinated and gadolinium-based) are safe compounds that are well-tolerated by most patients. However, a small percentage of patients exhibit contrast medium-induced adverse drug reactions that are dose-dependent and predictable (type A) or an even smaller cohort experience so-called type B (dose-independent, non-predictable). To increase patients' safety, recommendations/guidelines have been put forth in the literature and advice passed down informally by radiologists in practice to ensure contrast media safety. Through these, both reasonable suggestions as well as misinterpretations and myths (such as the misleading terms "allergy-like" reactions, and "iodine-allergy", the wrong assumption that the initial contact to a contrast medium could not induce an allergy, the estimation that an anti-allergy premedication could suppress all possible adverse reactions, and interleukin-2 as a risk/trigger for contrast medium adverse events) have arisen. Since the latter are not only unhelpful but also potentially reduce patients' safety, such myths and misconceptions are the focus of this review.

Quantification of absolute peripheral white blood cells and their subsets in patients with lupus erythematosus: comparison with other inflammatory diseases with and without autoimmune background.

To test the value of decreased peripheral leuko-/lymphocytes as screening test for the diagnosis lupus erythematosus (LE). Laboratory routine analyses, and flow cytometry (CD3, CD4, CD8) have been performed in 124 LE-patients. Other subjects included 57 healthy controls, 130 patients with non-autoimmune inflammatory diseases (dermatitis, psoriasis), and 17 patients with another autoimmune disease (progressive systemic sclerosis [PSS]). Numbers of peripheral blood leukocytes (P<0.0005), lymphocytes (P<0.00002), CD3+, and CD3+ CD4+ cells from LE-patients were significantly lower than from controls, patients either with dermatitis, psoriasis or PSS. CD3+ CD8+ cells were significantly diminished in patients with LE and PSS. Decreased numbers of white blood cells, lymphocytes and some of their subsets seem to indicate LE. Patients with PSS only had decreased T-cytotoxic cells. Inflammatory dermatoses lacking the autoimmunity as background have normal cell counts. For screening purpose absolute values of the mentioned blood cell subsets seem to be useful to distinguish both autoimmunity from non-autoimmune inflammatory diseases, and LE from PSS.

A possible role for cysteinyl-leukotrienes in non-ionic contrast media induced adverse reactions.

PURPOSE: To test whether mono- or dimeric X-ray contrast media (CM) may induce the de novo production of cysteinyl-leukotriens (cys-LT), that could contribute to allergic/allergy-like side effects. MATERIALS AND METHODS: Leukocytes from 39 patients receiving iopromide or iotrolan for routine CT-examination were analyzed for the production of cys-LT. Histamine levels were analyzed in plasma specimens. One patient with a positive history of a previous CM-reaction did not receive CM-injection. RESULTS: Three patients of the iopromide and five of the iotrolan group showed adverse reactions. Reactors had increased cys-LT values in samples obtained before CM-injection induced by the positive control (anti-FcepsilonRI antibodies) (6763.7 pg/ml+/-1367.3 versus 2299.8 pg/ml+/-399.2; p<0.007). Patients with versus without CM-reaction did not differ significantly with respect to their histamine values before CM-administration. In vitro iopromide (p<0.0002) and iotrolan (p<0.0008) induced significant cys-LT production as compared to IL-3 stimulation. In vivo both CM induced a significant increase 6h after CM administration (p<0.05). CONCLUSION: Our findings suggest that both CM seem to induce cys-LT production. As to whether the observed increased values in pre-dose samples of patients with as compared to those without reactions could contribute to identify high risk patients should be investigated in larger patient groups in future.