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1.
Int J Cardiovasc Imaging ; 38(9): 2003-2012, 2022 Sep.
Article in English | MEDLINE | ID: mdl-37726601

ABSTRACT

Follow-up after acute myocarditis is important to detect persisting myocardial dysfunction. However, recovery of atrial function has not been evaluated after acute myocarditis so far. Thirty-five patients with strictly defined acute myocarditis underwent cardiovascular magnetic resonance (CMR, 1.5 T) in the acute stage at baseline (BL) and at 3 months follow-up (FU). The study population included 13 patients with biopsy-proven "cardiomyopathy-like" myocarditis (CLM) and 22 patients with "infarct-like" (ILM) clinical presentation. CMR feature tracking (FT) was performed on conventional cine SSFP sequences. Median LA-GLS increased from 33.2 (14.5; 39.2) at BL to 37.0% (25.2; 44.1, P = 0.0018) at FU in the entire study population. Median LA-GLS also increased from 36.7 (26.5; 42.3) at BL to 41.3% (34.5; 44.8, P = 0.0262) at FU in the ILM subgroup and from 11.3 (6.4; 21.1) at BL to 21.4% (14.2; 30.7, P = 0.0186) at FU in the CLM subgroup. Median RA-GLS significantly increased from BL with 30.8 (22.5; 37.0) to FU with 33.7% (26.8; 45.4, P = 0.0027) in the entire study population. Median RA-GLS also significantly increased from 32.7 (25.8; 41.0) at BL to 35.8% (27.7; 48.0, P = 0.0495) at FU in the ILM subgroup and from 22.8 (13.1; 33.9) at BL to 31.0% (26.0; 40.8, P = 0.0266) at FU in the CLM subgroup. Our findings demonstrate recovery of LA and RA function by CMR-FT strain analyses in patients after acute myocarditis independent from clinical presentation. Monitoring of atrial strain could be an important tool for an individual assessment of healing after acute myocarditis.


Subject(s)
Myocarditis , Humans , Myocarditis/diagnostic imaging , Predictive Value of Tests , Magnetic Resonance Imaging , Atrial Function , Magnetic Resonance Spectroscopy
2.
Allergy ; 73(5): 1013-1021, 2018 05.
Article in English | MEDLINE | ID: mdl-29121407

ABSTRACT

BACKGROUND: Profilins are dominant pan-allergens known to cause cross-sensitization, leading to clinical symptoms such as pollen-food syndrome. This study aimed to determine the T-cell response to Phl p 12 in profilin-sensitized patients, by measuring the prevalence, strength and cross-reactivity to clinically relevant profilins. METHODS: The release of Phl p allergens from pollen was determined by mass spectrometry and immunochemistry. T-cell responses, epitope mapping and cross-reactivity to profilins (Phl p 12, Ole e 2, Bet v 2 and Mal d 4) were measured in vitro using PBMCs from 26 Spanish grass-allergic donors IgE-sensitized to profilin. Cross-reactivity was addressed in vivo using 2 different mouse strains (BALB/c and C3H). RESULTS: Phl p 12 and Phl p 1 are released from pollen simultaneously and in similar amounts. Both T-cell response frequency (17/26 donors) and strength were comparable between Phl p 12 and Phl p 1. T-cell cross-reactivity to other profilins correlated with overall sequence homology, and 2 immunodominant epitope regions of Phl p 12 were identified. Data from mice immunized with Phl p 12 showed that cross-reactivity to Bet v 2 was mediated by conserved epitopes and further influenced by additional genetic factors, likely to be MHC II. CONCLUSION: The strength, prevalence and cross-reactivity of T-cell responses towards Phl p 12 are comparable to the major allergen Phl p 1, which supports the hypothesis that T cells to Phl p 12 can play an important role in development of allergic symptoms, such as those associated with pollen-food syndrome.


Subject(s)
Allergens/immunology , Immunoglobulin E/immunology , Pollen/immunology , Profilins/immunology , T-Lymphocytes/immunology , Adolescent , Adult , Animals , Antigens, Plant , Cross Reactions , Female , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C3H , Middle Aged , Plant Proteins/immunology , Spain , Young Adult
3.
Eur Heart J Cardiovasc Imaging ; 18(7): 744-751, 2017 Jul 01.
Article in English | MEDLINE | ID: mdl-28329275

ABSTRACT

AIMS: Monitoring disease activity in myocarditis is important for tailored therapeutic strategies. This study evaluated the ability of T1 and T2 mapping cardiovascular magnetic resonance (CMR) to monitor the course of myocardial inflammation in healing myocarditis. METHODS AND RESULTS: Forty-eight patients with strictly defined acute myocarditis underwent CMR at 1.5 T in the acute stage, at 3-months (n = 39), and at 12-months follow-up (FU) (n = 21). Normal values were obtained in a control group of 27 healthy subjects. The CMR protocol included standard ('Lake-Louise') sequences as well as T1 (modified Look-Locker inversion recovery sequence, MOLLI) and T2 (gradient- and spin-echo sequence, GraSE) mapping. T1, T2, and extracellular volume (ECV) maps were generated using an OsiriX plug-in. Native myocardial T1, T2, and ECV values were increased in the acute stage, but declined with healing of myocarditis. The performances of global native T1 and T2 to differentiate acute from healed myocarditis stages were significantly better compared with all other global CMR parameters with AUCs of 0.85 (95% CI, 0.76-0.94) and 0.83 (95% CI, 0.73-0.93). Furthermore, regional native T1 and T2 in myocarditis lesions provided AUCs of 0.97 (95% CI, 0.93-1.02) and 0.93 (95% CI, 0.85-1.01), which were significantly superior to any other global or regional CMR parameter. CONCLUSION: Healing of myocarditis can be monitored by native myocardial T1 and T2 measurements without the need for contrast media. Both native myocardial T1 and T2 provide an excellent performance for assessing the stage of myocarditis by CMR.


Subject(s)
Image Interpretation, Computer-Assisted/methods , Magnetic Resonance Imaging, Cine/methods , Myocarditis/diagnostic imaging , Myocarditis/physiopathology , Aged , Area Under Curve , Case-Control Studies , Female , Humans , Male , Middle Aged , Monitoring, Physiologic/methods , Predictive Value of Tests , Prognosis , Prospective Studies , Recovery of Function , Reference Values , Severity of Illness Index
4.
Rofo ; 188(10): 933-9, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27433968

ABSTRACT

PURPOSE: To evaluate the accuracy of automatic plaque detection and the interobserver agreement of automatic versus manually adjusted quantification of coronary plaques on coronary CT angiography (cCTA) using commercially available software. MATERIALS AND METHODS: 10 cCTA datasets were evaluated using plaque software. First, the automatically detected plaques were verified. Second, two observers independently performed plaque quantification without revising the automatically constructed plaque contours (automatic approach). Then, each observer adjusted the plaque contours according to plaque delineation (adjusted approach). The interobserver agreement of both approaches was analyzed. RESULTS: 32 of 114 automatically identified findings were true-positive plaques, while 82 (72 %) were false-positive. 20 of 52 plaques (38 %) were missed by the software (false-negative). The automatic approach provided good interobserver agreement with relative differences of 0.9 ±â€Š16.0 % for plaque area and -3.3 ±â€Š33.8 % for plaque volume. Both observers independently adjusted all contours because they did not represent the plaque delineation. Interobserver agreement decreased for the adjusted approach with relative differences of 25.0 ±â€Š24.8 % for plaque area and 20.0 ±â€Š40.4 % for plaque volume. CONCLUSION: The automatic plaque analysis software is of limited value due to high numbers of false-positive and false-negative plaque findings. The automatic approach was reproducible but it necessitated adjustment of all constructed plaque contours resulting in deterioration of the interobserver agreement. KEY POINTS: • Automatic plaque detection is limited due to high false-positive and false-negative findings.• Automatic plaque quantification was reproducible in the few accurately detected plaques.• The automatically constructed contours did not represent the plaque delineation.• Both observers independently adjusted the plaque contours.• Manual adjustment of plaque contours reduced the interobserver agreement. Citation Format: • Laqmani A, Klink T, Quitzke M et al. Accuracy of Coronary Plaque Detection and Assessment of Interobserver Agreement for Plaque Quantification Using Automatic Coronary Plaque Analysis Software on Coronary CT Angiography. Fortschr Röntgenstr 2016; 188: 933 - 939.


Subject(s)
Carotid Stenosis/diagnostic imaging , Computed Tomography Angiography/methods , Coronary Angiography/methods , Pattern Recognition, Automated/methods , Radiographic Image Interpretation, Computer-Assisted/methods , Software , Aged , Algorithms , False Negative Reactions , False Positive Reactions , Female , Humans , Male , Middle Aged , Observer Variation , Radiographic Image Enhancement/methods , Reproducibility of Results , Sensitivity and Specificity
5.
Clin Exp Allergy ; 46(3): 439-48, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26436865

ABSTRACT

BACKGROUND: Allergen-specific immunotherapy is the only curative treatment for type I allergy. It can be administered subcutaneously (SCIT) or sublingually (SLIT). The clinical efficacy of these two treatment modalities appears to be similar, but potential differences in the immunological mechanisms involved have not been fully explored. OBJECTIVE: To compare changes in the allergen-specific T cell response induced by subcutaneous vs. sublingual administration of allergen-specific immunotherapy (AIT). METHODS: Grass pollen-allergic patients were randomized into groups receiving either SCIT injections or SLIT tablets or neither. PBMCs were tested for Timothy grass (TG)-specific cytokine production by ELISPOT after in vitro expansion with TG-peptide pools. Phenotypic characterization of cytokine-producing cells was performed by FACS. RESULTS: In the SCIT group, decreased IL-5 production was observed starting 10 months after treatment commenced. At 24 months, T cell responses showed IL-5 levels significantly below the before-treatment baseline. No significant reduction of IL-5 was observed in the SLIT or untreated group. However, a significant transient increase in IL-10 production after 10 months of treatment compared to baseline was detected in both treatment groups. FACS analysis revealed that IL-10 production was associated with CD4(+) T cells that also produced IFNγ and therefore may be associated with an IL-10-secreting type 1 cell phenotype. CONCLUSION AND CLINICAL RELEVANCE: The most dominant immunological changes on a cellular level were a decrease in IL-5 in the SCIT group and a significant, transient increase of IL-10 observed after 10 months of treatment in both treated groups. The distinct routes of AIT administration may induce different immunomodulatory mechanisms at the cellular level.


Subject(s)
Allergens/immunology , Hypersensitivity/immunology , Hypersensitivity/therapy , Sublingual Immunotherapy , T-Lymphocytes/immunology , Adult , Case-Control Studies , Cytokines/metabolism , Desensitization, Immunologic/methods , Female , Humans , Hypersensitivity/metabolism , Immunoglobulin E/blood , Immunoglobulin E/immunology , Male , Middle Aged , Poaceae/adverse effects , Pollen/immunology , Sublingual Immunotherapy/methods , T-Lymphocytes/metabolism , Young Adult
6.
Rofo ; 187(11): 1022-8, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26098252

ABSTRACT

PURPOSE: Patients with Marfan syndrome require repeated imaging for monitoring of aortic root aneurysms. Therefore, we evaluated the agreement and reproducibility of cine-MRI and echocardiography measurements of the sinuses of Valsalva in patients with suspected Marfan syndrome. MATERIALS AND METHODS: 51 consecutive patients with suspected Marfan syndrome were prospectively examined using cine-MRI and echocardiography. Two readers independently measured aortic root diameters at the level of the sinuses of Valsalva in both cine-MRI and echocardiography. Statistics included intraclass correlation coefficient, Pearson correlation coefficient, Bland-Altman analysis, and two-sided t-test. RESULTS: In 38 of the 51 individuals (74.5 %), the diagnosis of Marfan syndrome was established according to the criteria of the Ghent-2 nosology. Cine-MRI measurements of the sinuses of Valsalva revealed a strong correlation with echocardiography (r = 0.929), but a statistically significant bias of -1.0  mm (p < 0.001). The mean absolute diameter for sinuses of Valsalva obtained by cine-MRI was 32.3  ±  5.8 mm as compared to 33.4  ±  5.4 mm obtained by echocardiography. Interobserver agreement of measurements of the sinuses of Valsalva was higher for cine-MRI than for echocardiography (p = 0.029). CONCLUSION: Despite small, but statistically significant differences in terms of agreement and reproducibility, cine-MRI and echocardiographic measurements of aortic root diameters provide comparable results without a significant clinical difference. Therefore both techniques may be used for monitoring of the aortic root in patients with Marfan syndrome.


Subject(s)
Aorta/pathology , Echocardiography/methods , Magnetic Resonance Imaging, Cine/methods , Marfan Syndrome/diagnosis , Sinus of Valsalva/pathology , Adult , Female , Humans , Male , Middle Aged , Observer Variation , Sensitivity and Specificity , Statistics as Topic
7.
J Anim Sci ; 92(9): 3811-5, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25085402

ABSTRACT

A variety of biological materials are suitable for the analysis of bovine DNA. The objective of this study was to evaluate the ease of collection, storage, and cost as well as quality and quantity of DNA samples obtained from Bos taurus (European cattle) and Bos grunniens (yak) using 2 different sample types: whole blood sampling and nasal swabs. Hair follicle DNA samples from yaks were also analyzed. Deoxyribonucleic acid samples were collected from 1 herd of Black Angus yearling bulls (n = 166) and 1 herd of yaks (n = 24). A NanoDrop Bioanalyzer ND1000 was used to quantify DNA. To assess DNA purity, absorbance ratios were determined at wavelengths of 260 nm relative to 280 nm and 260 nm relative to 230 nm. Single nucleotide polymorphism genotyping was performed using a competitive allele-specific PCR (KASP) genotyping system and the call rates to 3 specific SNP were compared. Using a commercially available nonautomated ethanol DNA extraction technique, nasal swabs yielded a greater quantity of DNA than blood (P < 0.0001) and a greater quality DNA sample than blood (P < 0.0001). Blood and nasal swab performance in SNP genotyping assays were similar (P = 0.5). The greater expense of nasal swabs was offset by their ease of use: less time, skill, and equipment was needed to obtain a sample and the storage of samples was more convenient (room temperature). In yaks, accessing the coccygeal vein, which is relatively straightforward in cattle, was difficult. Nasal swabbing and hair follicle sampling in yaks was performed relatively easily. Yak hair follicles were a poor source of DNA. In conclusion, DNA collection using nasal swabs was more convenient and provided a greater quantity of DNA and better quality sample than blood collection in both Angus and yak. Notably, yak hair was a poor source of DNA, and yak blood was difficult to obtain.


Subject(s)
Cattle/blood , Cattle/genetics , DNA , Specimen Handling , Animals , Male , Polymerase Chain Reaction/methods , Polymorphism, Single Nucleotide , Species Specificity
8.
Clin Exp Allergy ; 44(3): 417-28, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24734285

ABSTRACT

BACKGROUND: IgE-mediated allergic rhinitis to grass pollen can successfully be treated with either allergen immunotherapy tablets (SLIT tablet) or SQ-standardized subcutaneous immunotherapy (SCIT). The efficacy of these two treatment modalities for grass allergy is comparable, but the immunological mechanisms may differ. ClinicalTrials.gov ID: NCT01889875. OBJECTIVES: To compare the immunological changes induced by SQ-standardized SCIT and SLIT tablet. METHODS: We randomized 40 individuals with grass pollen rhinitis into groups receiving SCIT, SLIT tablet, or neither and followed them for 15 months with regular serum measurements of specific IgE, IgG4, IgE-blocking factor, facilitated antigen presentation (FAP), and basophil activation test (BAT). Nasal challenges were used to assess changes in nasal sensitivity. RESULTS: After 15 months of treatment IgG4, IgE-blocking factor, FAP, and BAT values differed significantly in both SCIT and SLIT-tablet treatment groups when compared to the control group. Both SCIT and SLIT-tablet groups were significantly different from the control group after 1­3 months of treatment. In general, the changes induced by SCIT reached twice that of SLIT tablet, with the exception of specific IgE where SLIT tablet induced initial threefold increase compared with SCIT. A slight but significant increase in IgE and BAT after season was seen only in the control group. Significant differences between SCIT and SLIT tablet were observed early, but the differences diminished with the length of treatment, especially for FAP inhibition. CONCLUSIONS: Both SCIT and SLIT tablet induce significant changes in specific antibodies (IgE and IgG4) and competition assays (IgE-blocking factor, FAP, and BAT). Overall, SCIT induced larger (two- to threefold) changes than SLIT tablet, with the exception of FAP, where SLIT tablet showed a gradual increase ending at the same level as SCIT. Maximal change was generally reached after 3 months' treatment.


Subject(s)
Allergens/administration & dosage , Allergens/immunology , Desensitization, Immunologic , Poaceae/adverse effects , Pollen/immunology , Rhinitis, Allergic, Seasonal/immunology , Rhinitis, Allergic, Seasonal/therapy , Antibody Specificity/immunology , Antigen Presentation/immunology , Antigens, Plant/immunology , Basophils/immunology , Humans , Immunoglobulin E/blood , Immunoglobulin E/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Injections, Subcutaneous , Nasal Mucosa/immunology , Rhinitis, Allergic, Seasonal/diagnosis , Skin Tests , Tablets
9.
Rofo ; 186(10): 951-8, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24648233

ABSTRACT

PURPOSE: Percutaneous mitral valve repair with the MitraClip device (Abbott Vascular, Redwood City, California, USA) is a novel therapeutic option in patients with mitral regurgitation. This study evaluated the feasibility of cardiac volume measurements by cardiovascular magnetic resonance imaging (CMR) to assess reverse myocardial remodeling in patients after MitraClip implantation. MATERIALS AND METHODS: 12 patients underwent CMR at baseline (BL) before and at 6 months follow-up (FU) after MitraClip implantation. Cine-CMR was performed in short- and long-axes for the assessment of left ventricular (LV), right ventricular (RV) and left atrial (LA) volumes. RESULTS: Assessment of endocardial contours was not compromised by the device-related artifact. No significant differences in observer variances were observed for LV, RV and LA volume measurements between BL and FU. LV end-diastolic (median 127 [IQR 96 - 150] vs. 112 [86 - 150] ml/m(2); p = 0.03) and LV end-systolic (82 [54 - 91] vs. 69 [48 - 99] ml/m(2); p = 0.03) volume indices decreased significantly from BL to FU. No significant differences were found for RV end-diastolic (94 [75 - 103] vs. 99 [77 - 123] ml/m(2); p = 0.91), RV end-systolic (48 [42 - 80] vs. 51 [40 - 81] ml/m(2); p = 0.48), and LA (87 [55 - 124] vs. 92 [48 - 137] ml/m(2); p = 0.20) volume indices between BL and FU. CONCLUSION: CMR enables the assessment of cardiac volumes in patients after MitraClip implantation. Our CMR findings indicate that percutaneous mitral valve repair results in reverse LV but not in RV or LA remodeling. KEY POINTS: • Volume measurements by cardiovascular magnetic resonance imaging are feasible following percutaneous mitral valve repair despite device-related artifacts.• A significant reduction of left ventricular volume was found in terms of beneficial, reverse left ventricular remodeling after 6-month follow-up.• No significant reduction was found in right ventricular or left atrial volumes after percutaneous mitral valve repair after 6-month follow-up.


Subject(s)
Cardiac Catheterization/instrumentation , Cardiac Catheterization/methods , Image Interpretation, Computer-Assisted , Magnetic Resonance Imaging, Cine , Magnetic Resonance Imaging , Minimally Invasive Surgical Procedures/instrumentation , Minimally Invasive Surgical Procedures/methods , Mitral Valve Insufficiency/surgery , Mitral Valve/surgery , Postoperative Complications/diagnosis , Surgical Instruments , Ventricular Remodeling/physiology , Artifacts , Cardiac Volume/physiology , Echocardiography , Equipment Design , Feasibility Studies , Female , Follow-Up Studies , Heart Atria/physiopathology , Heart Ventricles/physiopathology , Humans , Male , Postoperative Complications/physiopathology
10.
Clin Exp Immunol ; 176(3): 310-9, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24528247

ABSTRACT

Allergen-specific immunotherapy (SIT) is a clinically effective therapy for immunoglobulin (Ig)E-mediated allergic diseases. To reduce the risk of IgE-mediated side effects, chemically modified allergoids have been introduced. Furthermore, adsorbance of allergens to aluminium hydroxide (alum) is widely used to enhance the immune response. The mechanisms behind the adjuvant effect of alum are still not completely understood. In the present study we analysed the effects of alum-adsorbed allergens and allergoids on their immunogenicity in vitro and in vivo and their ability to activate basophils of allergic donors. Human monocyte derived dendritic cells (DC) were incubated with native Phleum pratense or Betula verrucosa allergen extract or formaldehyde- or glutaraldehyde-modified allergoids, adsorbed or unadsorbed to alum. After maturation, DC were co-cultivated with autologous CD4(+) T cells. Allergenicity was tested by leukotriene and histamine release of human basophils. Finally, in-vivo immunogenicity was analysed by IgG production of immunized mice. T cell proliferation as well as interleukin (IL)-4, IL-13, IL-10 and interferon (IFN)-γ production were strongly decreased using glutaraldehyde-modified allergoids, but did not differ between alum-adsorbed allergens or allergoids and the corresponding unadsorbed preparations. Glutaraldehyde modification also led to a decreased leukotriene and histamine release compared to native allergens, being further decreased by adsorption to alum. In vivo, immunogenicity was reduced for allergoids which could be partly restored by adsorption to alum. Our results suggest that adsorption of native allergens or modified allergoids to alum had no consistent adjuvant effect but led to a reduced allergenicity in vitro, while we observed an adjuvant effect regarding IgG production in vivo.


Subject(s)
Adjuvants, Immunologic , Allergens/immunology , Aluminum Hydroxide/immunology , Plant Extracts/immunology , Allergens/chemistry , Allergoids , Alum Compounds/toxicity , Aluminum Hydroxide/chemistry , Animals , Apoptosis/genetics , Apoptosis/immunology , Basophils/immunology , Basophils/metabolism , Cytokines/biosynthesis , Dendritic Cells/drug effects , Dendritic Cells/immunology , Female , Histamine Release/immunology , Humans , Immunoglobulin G/immunology , Leukotrienes/metabolism , Lymphocyte Activation/immunology , Mice , Plant Extracts/chemistry , T-Lymphocyte Subsets/immunology
11.
Scand J Immunol ; 78(4): 352-6, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23790102

ABSTRACT

The function of cultured mast cells may depend on genetic or environmental influence on the stem cell donor. This study investigates whether asthma or atopy in the donor influenced the growth and sensitivity of mast cells cultured from patients with asthma and healthy controls under identical conditions. Mast cells were cultured from peripheral blood from twelve patients with an objectively confirmed asthma diagnosis and eight healthy subjects. During the last 2 weeks of culture, mast cells were incubated with IL-4 and 80 kU/l recombinant human IgE containing two clones (7% + 7%) specific for mite allergen Der p2. The sensitivity of IgE-mediated activation of mast cells was investigated as FcεRI-mediated upregulation of CD63. Ten subjects were atopic, defined as a positive skin prick test (>3 mm) to at least one of ten common allergens. After activation with recombinant Der p2, the maximum CD63 median fluorescence intensity was 20 456 ± 1640 (SE) for patients with asthma and 22,275 ± 1971 (SE) for controls (ns). The fraction of CD63 positive cells was 54.4% in patients with asthma and 48.4% in controls (ns). The allergen concentration inducing 50% of the maximal CD63 response was similar in patients with asthma [-0.4795 log ng/ml ± 0.092 (SE)] and controls (-0.6351 log ng/ml ± 0.083, ns) and in atopic and non-atopic subjects. When cultured, sensitized and activated under identical conditions, mast cells from allergic asthmatics and healthy controls respond similar. Activation of cultured mast cells appears to depend on culture conditions (IL-4, IgE) rather than on donor status as atopy and asthma.


Subject(s)
Antigens, Dermatophagoides/immunology , Arthropod Proteins/immunology , Asthma/immunology , Hypersensitivity, Immediate/immunology , Mast Cells/immunology , Adult , Antigens, Dermatophagoides/genetics , Arthropod Proteins/genetics , Asthma/metabolism , Asthma/pathology , Cells, Cultured , Female , Humans , Immunoglobulin E/immunology , Interleukin-4/immunology , Male , Mast Cells/metabolism , Middle Aged , Recombinant Proteins/immunology , Skin Tests , Tetraspanin 30/immunology , Tetraspanin 30/metabolism , Young Adult
12.
Radiologe ; 53(4): 300-1, 2013 Apr.
Article in German | MEDLINE | ID: mdl-23443905
13.
Rofo ; 184(12): 1131-7, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23023228

ABSTRACT

PURPOSE: To study the agreement between experienced and inexperienced observers before and after training using a standardized evaluation protocol for cardiac magnetic resonance imaging (CMR) measurements of left ventricular (LV) volumes, mass and infarct size. MATERIALS AND METHODS: First, 10 CMR studies from patients with myocardial infarction were analyzed by 2 experienced and 4 inexperienced observers in respect to end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF), LV mass and infarct size. Subsequently, the inexperienced observers were trained using a standardized evaluation protocol. Thereafter, all observers analyzed another 10 CMR studies. RESULTS: Before training the relative difference between experienced and inexperienced observers was -4.3±8.2% for EDV, -13.3±14.2% for ESV, 5.9±8.2% for EF, -12.2±10.9% for LV mass and -27.0±29.0% for infarct size in gram. After training, agreement significantly improved to 0.2±8.8% for EDV (p<0.05), -2.1±10.9 for ESV (p<0.01), 1.5±6.9% for EF (p<0.05), and -3.6±17.1% for infarct size (p<0.0001), but no improvement was seen for LV mass (-11.2±7.9, p=0.64). A slice based analysis showed, that the variable inclusion of the most basal and apical slices were mainly responsible for the low agreement of the measurements before training. CONCLUSION: Training using a standardized evaluation protocol significantly improved the agreement between experienced and inexperienced observers for important CMR parameters. The proposed evaluation protocol can be used for training to improve the reproducibility of CMR measurements.


Subject(s)
Cardiac Volume/physiology , Cardiology/education , Heart Ventricles/pathology , Image Interpretation, Computer-Assisted/methods , Inservice Training , Internship and Residency , Magnetic Resonance Imaging/methods , Myocardial Infarction/classification , Myocardial Infarction/diagnosis , Radiology/education , Students, Medical , Aged , Curriculum , Diastole/physiology , Female , Germany , Humans , Male , Middle Aged , Observer Variation , Papillary Muscles/pathology , Prognosis , Reference Standards , Reproducibility of Results , Stroke Volume/physiology , Systole/physiology
14.
Clin Exp Allergy ; 42(9): 1356-68, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22925322

ABSTRACT

BACKGROUND: Subcutaneous specific immunotherapy (SCIT) has proven sustained clinical efficacy against allergy. The recommended regimen for SCIT is a gradual updosing over a period of weeks. Commonly, in commercial products for SCIT, the specific allergen is formulated with an adjuvant, most often in the form of aluminium hydroxide (AlOH). It has been shown that allergen-specific IgG antibodies are induced as a result of successful SIT. OBJECTIVE: To investigate the possibility of optimizing the formulation of AlOH-based grass-pollen allergy vaccines for SCIT in a way that allows for shorter updosing regimens while maintaining the immunogenicity of the vaccine. METHODS: Mice were immunized with various concentrations of Phleum pratense (Phl p) allergen extract and AlOH or a fixed dilution of the maintenance doses of one conventional and one alternatively formulated vaccine. The kinetics of Phl p-specific IgG antibody responses in serum and spleen T cell responses were determined. Allergenicity, measured as the ability of the formulations to activate human basophils, was also determined. In addition, human T cell responses and the expression of dendritic cell surface markers after vaccine challenge in vitro were analysed. RESULTS: Specific IgG antibody responses were shown to depend on the AlOH concentration, but not on the allergen concentrations. The immunogenicity of the conventional formulation and the alternative formulation was shown to be similar with regard to the in vivo-induced IgG and T cell responses. In contrast, the allergenicity of the alternative formulation was significantly reduced compared with the conventional formulation. CONCLUSION: The optimization of the formulation allows for administration of a lower dose of allergen while maintaining the immunogenicity of the product and at the same time reducing allergenicity. CLINICAL RELEVANCE: This study indicates that the optimization of the allergen and the adjuvant formulation could benefit the safety/efficacy profile and allow for shorter updosing.


Subject(s)
Adjuvants, Immunologic/administration & dosage , Allergens/immunology , Desensitization, Immunologic/methods , Poaceae/immunology , Pollen/immunology , Rhinitis, Allergic, Seasonal/therapy , Allergens/administration & dosage , Aluminum Hydroxide/immunology , Animals , Female , Humans , Immunoglobulin G/blood , Injections, Subcutaneous , Mice , Mice, Inbred BALB C , Phleum/immunology , Plant Extracts/administration & dosage , Plant Extracts/immunology , Rhinitis, Allergic, Seasonal/immunology , T-Lymphocytes/immunology , Treatment Outcome
16.
Clin Genet ; 81(4): 334-40, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22292420

ABSTRACT

In a clinical setting diagnosis, heritability, risk and outcome of human disease rely heavily on the use of markers present in specific tissues. In the past decade, the development of genome-wide, non-hypothesis driven methods to identify molecular markers associated with disease have led to the discovery of numerous genetic variations associated with specific human diseases, the majority of which map within non-coding regions of the genome. In parallel, whole-genome studies focused on the role of gene regulatory epigenetic modifications such as DNA methylation and histone modifications are providing a conceptual framework for understanding the functional significance of sequence variation in human disease. This review highlights selected recent development in epigenetics and discusses their implications with respect to the identification of functional or novel single nucleotide polymorphisms.


Subject(s)
DNA/genetics , Disease/genetics , Epigenesis, Genetic , Genetic Variation , Genome, Human , DNA Methylation , Epigenomics , Genetic Predisposition to Disease , Histones/metabolism , Humans
17.
Rofo ; 183(6): 554-60, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21487982

ABSTRACT

PURPOSE: The preoperative assessment of mechanical dyssynchrony can help to improve patient selection in candidates for cardiac resynchronization therapy (CRT). The present study compared the performance of velocity-encoded (VENC) MRI to cine-magnetic resonance imaging (MRI) for quantifying mechanical ventricular dyssynchrony. MATERIALS AND METHODS: VENC-MRI and cine-MRI were performed in 20 patients with heart failure NYHA class III and reduced ejection fraction (median: 24 %, interquartile range: 18 - 28 %) before CRT device implantation. The interventricular mechanical delay (IVMD) was assessed by VENC-MRI as the temporal difference between the onset of aortic and pulmonary flow. Intraventricular dyssynchrony was quantified by cine-MRI, using the standard deviation of time to maximal wall thickening in sixteen left ventricular segments (SDt-16). The response to CRT was assessed in a six-month follow-up. RESULTS: 14 patients (70 %) clinically responded to CRT. A similar accuracy was found to predict the response to CRT by measurements of the IVMD and SDt-16 (75 vs. 70 %; p = ns). The time needed for data analysis was significantly shorter for the IVMD at 1.69 min (interquartile range: 1.66 - 1.88 min) compared to 9.63 min (interquartile range: 8.92 - 11.63 min) for the SDt-16 (p < 0.0001). CONCLUSION: Measurements of the IVMD by VENC-MRI and the SDt-16 by cine-MRI provide a similar accuracy to identify clinical responders to CRT. However, data analysis of the IVMD is significantly less time-consuming compared to data analysis of the SDt-16.


Subject(s)
Heart Failure/diagnosis , Magnetic Resonance Imaging, Cine/standards , Magnetic Resonance Imaging/standards , Ventricular Dysfunction/diagnosis , Aged , Cardiac Resynchronization Therapy , Female , Heart Failure/pathology , Heart Failure/therapy , Humans , Male , Middle Aged , Predictive Value of Tests , Reproducibility of Results , Statistics as Topic/standards , Time Factors
18.
J Bone Joint Surg Br ; 92(1): 83-91, 2010 Jan.
Article in English | MEDLINE | ID: mdl-20044684

ABSTRACT

In order to compare the outcome from surgical repair and physiotherapy, 103 patients with symptomatic small and medium-sized tears of the rotator cuff were randomly allocated to one of the two approaches. The primary outcome measure was the Constant score, and secondary outcome measures included the self-report section of the American Shoulder and Elbow Surgeons score, the Short Form 36 Health Survey and subscores for shoulder movement, pain, strength and patient satisfaction. Scores were taken at baseline and after six and 12 months by a blinded assessor. Nine patients (18%) with insufficient benefit from physiotherapy after at least 15 treatment sessions underwent secondary surgical treatment. Analysis of between-group differences showed better results for the surgery group on the Constant scale (difference 13.0 points, p - 0.002), on the American Shoulder and Elbow surgeons scale (difference 16.1 points, p < 0.0005), for pain-free abduction (difference 28.8 degrees , p = 0.003) and for reduction in pain (difference on a visual analogue scale -1.7 cm, p < 0.0005).


Subject(s)
Arthroscopy/standards , Physical Therapy Modalities/standards , Rotator Cuff Injuries , Rotator Cuff/surgery , Adult , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Pain Measurement , Patient Satisfaction , Range of Motion, Articular , Severity of Illness Index , Treatment Outcome
19.
Rofo ; 182(1): 29-35, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19676014

ABSTRACT

PURPOSE: To compare the ability of delayed-enhancement magnetic resonance imaging (DE-MRI) and other MRI and clinical parameters to identify diseases mimicking stress cardiomyopathy (SCM). MATERIALS AND METHODS: The study included 14 consecutive patients fulfilling the American Heart Association (AHA) criteria for SCM with acute left ventricular dysfunction in the absence of coronary artery disease, triggered by psychological stress. The MRI protocol consisted of cine, T 2-weighted, first-pass-perfusion (FPP) and DE-MRI. RESULTS: Six patients with DE were classified as mimicking SCM (non-SCM) and 8 patients without DE as SCM. FPP defects were found in 4 patients with non-SCM and in none with SCM (p < 0.05). Myocardial edema was found in 5 patients with non-SCM and in 2 patients with SCM (p = ns). No significant differences in clinical findings such as ECG, cardiac markers and echocardiographic recovery of left ventricular function were found between patients with non-SCM and SCM. CONCLUSION: Non-SCM defined by DE-MRI is a frequent finding in patients fulfilling the AHA criteria for SCM. Clinical findings seem to be of limited value to differentiate between non-SCM and SCM.


Subject(s)
Image Enhancement/methods , Image Processing, Computer-Assisted/methods , Imaging, Three-Dimensional/methods , Magnetic Resonance Imaging, Cine/methods , Magnetic Resonance Imaging/methods , Takotsubo Cardiomyopathy/diagnosis , Aged , Contrast Media/administration & dosage , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Myocardial Contraction/physiology , Retrospective Studies , Sensitivity and Specificity , Stress, Psychological/complications , Stroke Volume/physiology , Ventricular Dysfunction, Left/diagnosis
20.
Rofo ; 181(2): 161-8, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19173155

ABSTRACT

PURPOSE: To evaluate a 3D model of the left ventricle (LV) which allows calculation of LV function parameters on the basis of both short axis (SA) and long axis (LA) cine acquisitions. Comparison with the conventional Simpson's rule method in a volunteer and patient collective. MATERIALS AND METHODS: Cine imaging was performed with a prospectively triggered SSFP sequence: trueFISP: TR 3.6 msec, TE 1.8 msec, bFFE: TR 3.0 msec, TE 1.4 msec, flip angle 60 degrees , resolution 1.37 x 1.37 mm, slice thickness 8 mm, gap 2 mm in SA orientation from apex to basis and in radial LA orientation (spacing 15 degrees) in 11 volunteers and 27 patients with mitral valve insufficiency. Five different volume computations were compared: Simpson's rule based on all SA slices (M0), 3D shape model based on all SA slices (M1a), 3D shape model based on 3 SA slices (M1b), 3D shape model based on all SA and LA slices (M2a), and 3D shape model based on 3 SA slices and 1 LA slice (M2b). RESULTS: M 0 and M 1a give similar results (r: 0.99, b: 0.98). M 2a produces larger volumes than M 0 (b: 0.85) due to the inclusion of the LA contours. M 1b effectively reproduces the volumes computed with M 0 (r: 0.99, b: 1.02). M 2b effectively reproduces the volumes computed with M 2a (r: 0.99, b: 0.94). M 2b and M 0 give similar results in the patient collective (r: 0.99, b: 0.97). CONCLUSION: The proposed 3D shape model allows merging of information acquired in different orientations and thus the combination of SA and LA contours with better coverage of the left ventricle. It provides a suitable fit with a reduced number of segmented contours.


Subject(s)
Heart Ventricles/anatomy & histology , Image Interpretation, Computer-Assisted/methods , Imaging, Three-Dimensional/methods , Magnetic Resonance Imaging, Cine/methods , Models, Anatomic , Models, Cardiovascular , Ventricular Function, Left/physiology , Adult , Computer Simulation , Female , Humans , Male , Reproducibility of Results , Sensitivity and Specificity
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