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1.
Toxicol In Vitro ; 30(1 Pt A): 176-84, 2015 Dec 25.
Article in English | MEDLINE | ID: mdl-25795400

ABSTRACT

Within the Predict-IV FP7 project a strategy for measurement of in vitro biokinetics was developed, requiring the characterization of the cellular model used, especially regarding biotransformation, which frequently depends on cytochrome P450 (CYP) activity. The extrahepatic in situ CYP-mediated metabolism is especially relevant in target organ toxicity. In this study, the constitutive mRNA levels and protein localization of different CYP isoforms were investigated in 3D aggregating brain cell cultures. CYP1A1, CYP2B1/B2, CYP2D2/4, CYP2E1 and CYP3A were expressed; CYP1A1 and 2B1 represented almost 80% of the total mRNA content. Double-immunolabeling revealed their presence in astrocytes, in neurons, and to a minor extent in oligodendrocytes, confirming the cell-specific localization of CYPs in the brain. These results together with the recently reported formation of an amiodarone metabolite following repeated exposure suggest that this cell culture system possesses some metabolic potential, most likely contributing to its high performance in neurotoxicological studies and support the use of this model in studying brain neurotoxicity involving mechanisms of toxication/detoxication.


Subject(s)
Brain/cytology , Cytochrome P-450 Enzyme System/metabolism , Neurons/metabolism , Aging , Animals , Cells, Cultured , Cytochrome P-450 Enzyme System/classification , Embryo, Mammalian/cytology , Gene Expression Regulation, Enzymologic , Hepatocytes , Isoenzymes , Protein Transport , Rats
2.
Toxicol In Vitro ; 27(4): 1357-76, 2013 Jun.
Article in English | MEDLINE | ID: mdl-22922246

ABSTRACT

ACuteTox is a project within the 6th European Framework Programme which had as one of its goals to develop, optimise and prevalidate a non-animal testing strategy for predicting human acute oral toxicity. In its last 6 months, a challenging exercise was conducted to assess the predictive capacity of the developed testing strategies and final identification of the most promising ones. Thirty-two chemicals were tested blind in the battery of in vitro and in silico methods selected during the first phase of the project. This paper describes the classification approaches studied: single step procedures and two step tiered testing strategies. In summary, four in vitro testing strategies were proposed as best performing in terms of predictive capacity with respect to the European acute oral toxicity classification. In addition, a heuristic testing strategy is suggested that combines the prediction results gained from the neutral red uptake assay performed in 3T3 cells, with information on neurotoxicity alerts identified by the primary rat brain aggregates test method. Octanol-water partition coefficients and in silico prediction of intestinal absorption and blood-brain barrier passage are also considered. This approach allows to reduce the number of chemicals wrongly predicted as not classified (LD50>2000 mg/kg b.w.).


Subject(s)
Neural Networks, Computer , Toxicity Tests, Acute , Administration, Oral , Animal Testing Alternatives , Animals , Blood-Brain Barrier/metabolism , Cell Line , Cell Survival , Colony-Forming Units Assay , Computer Simulation , Cytokines/metabolism , Humans , Intestinal Absorption , Lethal Dose 50 , Mice , Oxidative Stress , Rats , Risk Assessment
3.
Toxicol In Vitro ; 27(4): 1347-56, 2013 Jun.
Article in English | MEDLINE | ID: mdl-22951948

ABSTRACT

A comparative analysis of eight cytotoxicity assays [the 3T3 and normal human keratinocytes Neutral Red Uptake (NRU) assay, the primary rat hepatocytes, human HepG2 and 3T3 MTT assay, and the human A.704, SH-SY5Y and HepG2 cells propidium iodide (PI) assay] included in several work packages of the EU Integrated Project ACuteTox, has been carried out. The aim was to evaluate whether cells originating from liver, kidney and brain provided different in vitro acute toxicity results, and the influence of primary liver cells versus cell lines originated from the same tissue. Spearman rank correlation analysis and Hierarchical Cluster Analysis were performed based on the IC50 (50% inhibitory concentrations for the endpoint measured) values generated for 57 chemicals. A relatively large number of neurotoxicants and hepatotoxicants were included which allowed to examine the impact of chemicals with specific tissue toxicity on the results. Our analyses confirmed the similarity between the NRU assays and between the two hepatic cell systems related MTT assays. The type of assay appears to have the greatest influence upon the clustering result regardless of the origin of the cells used. The information provided by the NRU and MTT assays differed from that provided by the PI assay. This approach did not allow to show tissue specific toxicity but it does reveal the effectiveness of the clustering methodology for choosing assays for a testing program for predicting e.g. acute oral toxicity in humans.


Subject(s)
Toxicity Tests, Acute/methods , 3T3 Cells , Animals , Cell Line, Tumor , Cell Survival/drug effects , Cells, Cultured , Cytotoxins/toxicity , Hepatocytes/drug effects , Humans , Mice , Rats
5.
Toxicol In Vitro ; 27(4): 1377-94, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23178337

ABSTRACT

More than 50 different in vitro and in silico methods assessing specific organ- and system-toxicity, such as haemato-, neuro-, nephro- and hepatotoxicity, as well as intestinal absorption, distribution and metabolism, have been used in the first phase of the ACuteTox project to test a common set of 57 chemicals. This paper describes the methods used for statistical evaluation of concentration-response data collected for each of the endpoint assays, and for the development of a testing strategy applicable for acute toxicity classification of chemicals based on the achieved results of the concentration-response analysis. A final list of in vitro test methods considered to be promising candidates for building blocks of the testing strategy is presented. Only these selected test methods were further investigated in the prevalidation phase of the project. The test methods were chosen according to their reproducibility and reliability and most importantly, according to their potential to classify chemicals into the official acute oral toxicity categories of the EU Classification, Labelling and Packaging (CLP) Regulation. The potential of the test methods to correctly classify the chemicals was assessed by Classification and Regression Trees (CART) analysis.


Subject(s)
Toxicity Tests, Acute/methods , 3T3 Cells , Acetylcholinesterase/metabolism , Administration, Oral , Animals , Brain/metabolism , Caspase 3/genetics , Cell Line, Tumor , Cell Survival , Cells, Cultured , Colony-Forming Units Assay , Cytokines/metabolism , Data Interpretation, Statistical , Fetal Blood/cytology , Gene Expression , Hepatocytes , Humans , Lethal Dose 50 , Leukocytes, Mononuclear , Mice , Neural Networks, Computer , Neurons , RNA, Messenger/metabolism , Rats , Receptors, GABA/metabolism , Risk Assessment , Uridine/metabolism
6.
Toxicol Appl Pharmacol ; 260(3): 232-40, 2012 May 01.
Article in English | MEDLINE | ID: mdl-22414680

ABSTRACT

Embryo implantation is a crucial step in human reproduction and depends on the timely development of a receptive endometrium. The human endometrium is unique among adult tissues due to its dynamic alterations during each menstrual cycle. It hosts the implantation process which is governed by progesterone, whereas 17ß-estradiol regulates the preceding proliferation of the endometrium. The receptors for both steroids are targets for drugs and endocrine disrupting chemicals. Chemicals with unwanted antigestagenic actions are potentially hazardous to embryo implantation since many pharmaceutical antiprogestins adversely affect endometrial receptivity. This risk can be addressed by human tissue-specific in vitro assays. As working basis we compiled data on chemicals interacting with the PR. In our experimental work, we developed a flexible in vitro model based on human endometrial Ishikawa cells. Effects of antiprogestin compounds on pre-selected target genes were characterized by sigmoidal concentration-response curves obtained by RT-qPCR. The estrogen sulfotransferase (SULT1E1) was identified as the most responsive target gene by microarray analysis. The agonistic effect of progesterone on SULT1E1 mRNA was concentration-dependently antagonized by RU486 (mifepristone) and ZK137316 and, with lower potency, by 4-nonylphenol, bisphenol A and apigenin. The negative control methyl acetoacetate showed no effect. The effects of progesterone and RU486 were confirmed on the protein level by Western blotting. We demonstrated proof of principle that our Ishikawa model is suitable to study quantitatively effects of antiprogestin-like chemicals on endometrial target genes in comparison to pharmaceutical reference compounds. This test is useful for hazard identification and may contribute to reduce animal studies.


Subject(s)
Drug-Related Side Effects and Adverse Reactions , Embryo Implantation/drug effects , Endometrium/drug effects , Progesterone/metabolism , Toxicity Tests/methods , Adult , Blotting, Western , Cells, Cultured , Endocrine Disruptors/toxicity , Endometrium/metabolism , Female , Hormone Antagonists/toxicity , Humans , Oligonucleotide Array Sequence Analysis , Progesterone/pharmacology , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction/methods , Sulfotransferases/genetics
7.
J Biomater Appl ; 25(8): 771-93, 2011 May.
Article in English | MEDLINE | ID: mdl-20237180

ABSTRACT

Mesh implants are frequently used in congenital diaphragmatic hernia. This experimental study aimed to examine the influence of different materials on the diaphragmatic movement over time as well as their mechanical qualities after 4 months. Ultrapro®, Surgisis®, and Proceed® were implanted onto a diaphragmatic defect in growing rabbits. Diaphragmatic mobility was determined at three time points. At 4 months, defect shrinkage and mechanical properties were measured. The break strength decreased for Ultrapro® and Surgisis®, but did not change relevantly for Proceed®. Ultrapro® (32.46 N/cm) and Proceed® (31.75 N/cm) showed a four-fold higher resistance to tearing than Surgisis® (8.31 N/cm). The elasticity of Ultrapro® showed no significant difference compared to Surgisis® (p = 0.75). Proceed®, on the other hand, was more than twice as elastic as Ultrapro® or Surgisis® (p = 0.015). Ultrapro® had a higher spring rate (6.48 N/mm) compared to Surgisis® (3.82 N/mm) or Proceed® (5.23 N/mm). Observing the standardized movement rates of the diaphragm for each mesh group over time the only statistical differences were seen for the Proceed® group. On account of its material qualities Ultrapro® was found to be the most suitable mesh material for demanding locations in our model.


Subject(s)
Biocompatible Materials/chemistry , Diaphragm/physiopathology , Diaphragm/surgery , Elastic Modulus , Polypropylenes/chemistry , Surgical Mesh , Animals , Diaphragm/pathology , Materials Testing , Models, Animal , Polymers/chemistry , Postoperative Complications , Prostheses and Implants , Rabbits , Tensile Strength , Wound Healing
8.
J Biomater Appl ; 25(7): 721-41, 2011 Mar.
Article in English | MEDLINE | ID: mdl-20219847

ABSTRACT

Mesh implants as standard treatment for tissue defects can be adapted to patient's needs by specific bioactive coatings. The biophysical interaction with the surrounding tissue must be understood to describe the influence of coatings qualitatively and quantitatively. This study investigates the use of meshes to repair diaphragmatic defects. The physical stress in this tissue is high in comparison to other applications. Therefore, knowledge gained from this experimental model can be applied to other locations. Meshes were implanted on surgically created diaphragmatic defects in growing rabbits. A standardized load model was used to investigate 33 rabbits. The commercial products Ultrapro®, Surgisis®, and Proceed® were implanted. The adhesive properties of the meshes as well as the defect size were determined macroscopically at explantation after 4 months. Sections of the explanted meshes and diaphragms were examined histologically and immunohistochemically. The median defect size for all mesh groups decreased from the initial size of 10 mm down to 4.5 mm at explantation. No statistically significant differences were seen between the three mesh groups. Surgisis® was found to be completely disintegrated after 4 months. Ultrapro® and Proceed® showed no macroscopic differences compared to their original appearance. Both sealed the original diaphragmatic defect as tightly as at time of implantation. Histological and immunohistochemical analyses showed significant differences between the three mesh groups. Proceed® caused stronger inflammatory reaction in the surrounding tissue and inferior connective tissue formation. Regarding the composition of the newly generated tissue within the defect area, Ultrapro® and Surgisis® were found superior. This can sufficiently be explained by the different gradient of inflammatory reaction in the surrounding tissue. Because Surgisis® offers no sufficiently lasting support for the diaphragmatic defect, our future main focus for mesh modification is laid on Ultrapro®.


Subject(s)
Biocompatible Materials/metabolism , Hernia, Diaphragmatic/surgery , Surgical Mesh , Animals , Apoptosis , Biocompatible Materials/chemistry , Collagen/metabolism , Female , Hernia, Diaphragmatic/pathology , Rabbits , Stress, Mechanical , Wound Healing
9.
Neonatology ; 97(4): 311-7, 2010 Jun.
Article in English | MEDLINE | ID: mdl-19887862

ABSTRACT

BACKGROUND: Skin to skin care (SSC), prone (PP) and supine (SP) positions are standard positions in daily care for premature infants. Their influence on cardiorespiratory parameters and thermoregulation is discussed controversially. OBJECTIVES: We compared SSC with PP, the recommended position for preterm infants, and SP, the safest position for term infants, and tested the hypothesis that SSC has no impact on cardiorespiratory parameters and thermoregulation. METHODS: In 18 spontaneously breathing premature infants [median gestational 28 weeks (24-32); chronological age 36 days (7-64), and weight 1,543 g (750-2,100)], heart and respiratory rate, breathing pattern, episodes of desaturation (<85 but >or=80 and <80%), oxygen saturation and rectal temperature were analyzed with polygraphy (Alice 3(R) and 3.5(R)) in a 6-hour measuring cycle of three subsequent series (120 min each in SP, SSC and PP) and compared (Wilcoxon test). RESULTS: During SSC, we found no increase in apneic attacks and bradycardic episodes and no difference in respiratory rate, breathing pattern, oxygen saturation, episodes and duration of desaturation compared to SP and PP. Episodes of desaturation <85 but >or=80 and <80% were more frequent in SP compared to PP (p = 0.0421 and p = 0.0319). Heart rate increased in SSC and PP compared to SP (154.86 bpm, SD 11.55, and 153.33 bpm, SD 15.95 vs. 150.25 bpm, SD 14.64; p = 0.0013 and p = 0.0346). Temperature level was not significantly higher during SSC and PP compared to SP except a rise between the start and the end of the 6-hour measuring cycle (37.05 degrees C, SD 0.2 vs. 37.30 degrees C, SD 0.3; p = 0.0436). CONCLUSION: We found no significant SSC-mediated changes in quality and quantity of desaturations and in body temperature compared to PP in preterm infants.


Subject(s)
Body Temperature Regulation/physiology , Cardiovascular Physiological Phenomena , Infant, Premature/physiology , Prone Position/physiology , Respiratory Physiological Phenomena , Skin Physiological Phenomena , Supine Position/physiology , Apnea/prevention & control , Body Temperature/physiology , Bradycardia/prevention & control , Female , Heart Rate/physiology , Humans , Infant, Newborn , Male , Patient Positioning/methods , Respiration , Touch/physiology
10.
Rofo ; 181(9): 888-95, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19582654

ABSTRACT

PURPOSE: Since semi-automated lesion quantification may be more precise than manual uni- and bidimensional measurements, the purpose of this study was to compare semi-automated with manual evaluations of cervical, thoracic and abdominal lymph nodes in patients with malignant lymphoma. MATERIALS AND METHODS: 62 patients with known malignant lymphoma underwent staging with contrast-enhanced 16-MDCT (16x0.7 mm coll., 120 kV, cervical/thoracic/abdominal: 150/120/160 mAseff., 1/1.25 /1 pitch, 4/3 - 5/4 - 5/4 slice thickness/reconstruction increment). On the basis of these standard reconstructed slices, each lesion was quantified in terms of RECIST and its longest orthographic diameter using a semi-automated software tool (Syngo CT Oncology, Siemens Medical Solutions, Forchheim, Germany) and manually by an experienced radiologist. The degree of agreement between manual measurements and software quantification was statistically assessed by computing the concordance correlation coefficient kappa and represented graphically in corresponding Bland-Altman plots. RESULTS: 74/80 cervical, 51/80 thoracic and 75/80 abdominal lymph nodes were correctly evaluated by the software. A strong degree of agreement between both measurement techniques (RECIST diameter: kappa = 0.97 (cervical)/0.98 (thoracic)/0.99 (abdominal); longest orthographic diameter: kappa = 0.97/0.93/0.97) was obtained. CONCLUSION: Semi-automated measurement of cervical, thoracic and abdominal lymph nodes showed valid results on standard axial reconstructions compared to manual quantification with the limitation of a high false segmentation rate in thoracic lymph nodes.


Subject(s)
Abdominal Neoplasms/diagnostic imaging , Artificial Intelligence , Head and Neck Neoplasms/diagnostic imaging , Image Interpretation, Computer-Assisted/methods , Lymphography/methods , Lymphoma, Non-Hodgkin/diagnostic imaging , Radiography, Dual-Energy Scanned Projection/methods , Software , Thoracic Neoplasms/diagnostic imaging , Tomography, Spiral Computed/methods , Whole Body Imaging/methods , Adult , Aged , Aged, 80 and over , Algorithms , Contrast Media/administration & dosage , Female , Humans , Image Interpretation, Computer-Assisted/standards , Lymphography/standards , Male , Middle Aged , Radiography, Dual-Energy Scanned Projection/standards , Radiology Information Systems , Reference Values , Retrospective Studies , Sensitivity and Specificity , Tomography, Spiral Computed/standards , Whole Body Imaging/standards , World Health Organization
11.
Caries Res ; 43(4): 261-8, 2009.
Article in English | MEDLINE | ID: mdl-19439947

ABSTRACT

Although CO(2) laser irradiation can decrease enamel demineralisation, it has still not been clarified which laser wavelength and which irradiation conditions represent the optimum parameters for application as preventive treatment. The aim of the present explorative study was to find low-fluence CO(2) laser (lambda = 10.6 microm) parameters resulting in a maximum caries-preventive effect with the least thermal damage. Different laser parameters were systematically evaluated in 3 steps. In the first experiment, 5 fluences of 0.1, 0.3, 0.4, 0.5 and 0.6 J/cm(2), combined with high repetition rates and 10 micros pulse duration, were chosen for the experiments. In a second experiment, the influence of different pulse durations (5, 10, 20, 30 and 50 micros) on the demineralisation of dental enamel was assessed. Finally, 3 different irradiation times (2, 5 and 9 s) were tested in a third experiment. In total, 276 bovine enamel blocks were used for the experiments. An 8-day pH-cycling regime was performed after the laser treatment. Demineralisation was assessed by lesion depth measurements with a polarised light microscope, and morphological changes were assessed with a scanning electron microscope. Irradiation with 0.3 J/cm(2), 5 micros, 226 Hz for 9 s (2,036 overlapping pulses) increased caries resistance by up to 81% compared to the control and was even significantly better than fluoride application (25%, p < 0.0001). Scanning electron microscopy examination did not reveal any obvious damage caused by the laser irradiation.


Subject(s)
Dental Caries Susceptibility/radiation effects , Dental Caries/prevention & control , Dental Enamel/radiation effects , Hardness/radiation effects , Lasers, Gas/therapeutic use , Animals , Cattle , Cross-Sectional Studies , Laser Therapy/instrumentation , Laser Therapy/methods , Linear Models , Statistics, Nonparametric , Tooth Demineralization/prevention & control , Tooth Demineralization/radiotherapy
12.
Br J Radiol ; 81(971): 841-7, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18941043

ABSTRACT

The aim of the study was to evaluate the performance of a computer-aided detection (CAD) algorithm in low-dose and full-dose multidetector-row CT (MDCT) of the thorax and its impact on radiologists' performance. Chest CT examinations of 77 patients were evaluated retrospectively for pulmonary nodules. All patients had undergone a 16-slice MDCT chest examination with a standard acquisition protocol. Artificial image noise was added to the raw data to simulate image acquisition at 10 mAs(eff.) The data were transferred to dedicated lung analysis software (LungCare) with a prototype CAD algorithm (LungCAD). CAD was applied to both dose settings. Images were read by a radiologist and a first-year resident with and without the software at both dose settings. All images were reviewed in consensus by the two radiologists to set the reference standard. Sensitivity results with respect to the reference standard were compared. No statistically significant differences in the detection rate for all pulmonary nodules could be found between low-dose and full-dose settings for the CAD software alone (p = 0.0065). Both radiologists displayed a statistically significant increase in sensitivity with the use of CAD (p<0.0001). In conclusion, CAD is beneficial in both low-dose and standard-dose settings. This may be beneficial in reducing false-negative diagnosis in lung cancer screening, standard chest examinations and the search for metastases.


Subject(s)
Algorithms , Lung Neoplasms/diagnostic imaging , Radiographic Image Interpretation, Computer-Assisted/standards , Radiology/standards , Contrast Media/administration & dosage , Female , Humans , Image Enhancement/methods , Male , Middle Aged , Retrospective Studies , Sensitivity and Specificity , Tomography, X-Ray Computed/methods
13.
Allergy ; 63(11): 1521-8, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18925888

ABSTRACT

BACKGROUND: Component-resolved diagnostics using microarray technology has recently been introduced into clinical allergology, but its applicability in children with food allergy has hardly been investigated so far. The aim of this study was to evaluate the utility of microarray-based IgE detection in the diagnostic workup of food allergy and to compare this new diagnostic tool with established methods of allergen-specific IgE detection. METHODS: We investigated 130 infants and children with suspected allergy to cow's milk (CM) or hen's egg (HE). Serum IgE measurements, skin prick tests, allergen microarray assays and controlled oral food challenges with HE and CM were performed. RESULTS: We analyzed 145 oral challenges that served as reference parameters for assay performance assessment. On this basis, the panel of microarrayed allergen components was shown to represent a comprehensive repertoire of clinically relevant CM and HE proteins. Additionally, the implemented CM and HE components respectively sufficed for equivalent test performance as compared to the corresponding fluorescence enzyme immunoassay extract and skin testing. However, component-resolved diagnostics for HE and CM allergy did not make oral food challenges superfluous. Clinical IgE decision points predicting positive oral food challenges could be calculated for both in vitro test methods. CONCLUSIONS: Allergen microarrays provide a new tool to diagnose symptomatic CM and HE allergy. They show performance characteristics comparable to the current diagnostic tests and may be indicated in small children in whom only small blood volumes are obtainable. However, they are not capable of replacing double-blind, placebo-controlled food challenges in most cases.


Subject(s)
Egg Hypersensitivity/diagnosis , Immunoglobulin E/analysis , Milk Hypersensitivity/diagnosis , Protein Array Analysis , Child , Child, Preschool , Egg Proteins/immunology , Female , Humans , Infant , Logistic Models , Male , Milk Proteins/immunology , Retrospective Studies , Sensitivity and Specificity , Skin Tests
14.
Rofo ; 180(6): 540-6, 2008 Jun.
Article in German | MEDLINE | ID: mdl-18504665

ABSTRACT

PURPOSE: Retrospective evaluation of computer-aided detection software (CAD) for automated detection (LungCAD, Siemens Medical solutions, Forchheim, Germany) and volumetry (LungCARE) of pulmonary nodules in dose-reduced pediatric MDCT. MATERIALS AND METHODS: 30 scans of 24 children (10.4+/-5.9 years, 13 girls, 11 boys, 39.7+/-29.3 kg body weight) were performed on a 16-MDCT for tumor staging (n=18), inflammation (n=9), other indications (n=3). Tube voltage 120 kVp and effective mAs were adapted to body weight. Slice thickness 2 mm, increment 1 mm. A pediatric radiologist (U1), a CAD expert (U2) and an inexperienced radiologist (U3) independently analyzed the lung window images without and with the CAD as a second reader. In a consensus decision U 1 and U 2 were the reference standard. RESULTS: Five examinations had to be excluded from the study due to other underlying lung disease. A total of 24 pulmonary nodules were found in all data sets with a minimal diameter of 0.35 mm to 3.81 mm (mean 1.7+/-0.85 mm). The sensitivities were as follows: U1 95.8% and 100% with CAD; U2 91.7% U3 66.7%. U2 and U3 did not detect further nodules with CAD. The sensitivity of CAD alone was 41.7 % with 0.32 false-positive findings per examination. Interobserver agreement between U1 / U2 regarding nodule detection with CAD was good (k=0.6500) and without CAD very good (k=0.8727). For the rest (U1 /U3; U2 / U3 with and without CAD), it was weak (k=0.0667-0.1884). Depending on the measured value (axial measurement, volume), there is a significant correlation (p=0.0026-0.0432) between nodule size and CAD detection. Undetected pulmonary nodules (mean 1.35 mm; range 0.35-2.61 mm) were smaller than the detected ones (mean 2.19 mm; range 1.35-3.81 mm). No significant correlation was found between CAD findings and patient age (p=0.9263) and body weight (p=0.9271) as well as nodule location (subpleural, intraparenchymal; p=1.0) and noise/SNR. CONCLUSION: In our study with 2 mm slice thickness and very small lesion sizes, the analyzed CAD algorithm for detection and volumetry of pulmonary nodules has limited application in pediatric dose-reduced 16-MDCTs. Determination of lesion size is possible even in the case of false-negatives.


Subject(s)
Diagnosis, Computer-Assisted/methods , Image Processing, Computer-Assisted/methods , Lung Neoplasms/diagnostic imaging , Software Design , Solitary Pulmonary Nodule/diagnostic imaging , Tomography, Spiral Computed/methods , Adolescent , Algorithms , Child , Child, Preschool , Contrast Media/administration & dosage , Female , Humans , Infant , Iohexol/analogs & derivatives , Lung/diagnostic imaging , Male , Observer Variation , Sensitivity and Specificity
15.
Eur Radiol ; 18(8): 1690-5, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18392831

ABSTRACT

To compare the impact of iodine concentration using two different contrast materials (CM) at standardized iodine delivery rate (IDR) and overall iodine load in 16-multidetector-row-CT-angiography (MDCTA) of the pulmonary arteries of 192 patients with known or suspected pulmonary embolism. One hundred three patients (group A) received 148 ml of a CM containing 300 mg iodine/ml (Ultravist 300, BayerScheringPharma) at a flow rate of 4.9 ml/s. Eighty-nine patients (group B) received 120 ml of a CM with a concentration of 370 mg iodine/ml (Ultravist 370) at a flow rate of 4.0 ml/s, resulting in a standardized IDR (approximately 1.5 gI/s) and the same overall amount of iodine (44.4 g). Both CM injections were followed by a saline chaser. Mean density values were determined in the pulmonary trunk, the ascending and the descending aorta, respectively. Applying repeated-measures ANOVA, no statistically significant differences between both MDCTA protocols were found (p = 0.5790): the mean density in the pulmonary trunk was 355 +/- 116 Hounsfield Units (group A) and 358 +/- 115 (group B). The corresponding values for the ascending and descending aorta were 295 +/- 79 (group A) and 284 +/- 65 (group B) as well as 272 +/- 71 and 262 +/- 70. In conclusion, the use of standardized IDR and overall iodine load provides comparable intravascular CM density in pulmonary 16-MDCTA for delivering contrast materials with different iodine concentrations.


Subject(s)
Angiography/methods , Iohexol/analogs & derivatives , Pulmonary Artery/diagnostic imaging , Pulmonary Embolism/diagnostic imaging , Radiographic Image Enhancement/methods , Tomography, X-Ray Computed/methods , Contrast Media/administration & dosage , Dose-Response Relationship, Drug , Female , Humans , Injections, Intra-Arterial , Iohexol/administration & dosage , Male , Middle Aged , Pulmonary Artery/drug effects , Reproducibility of Results , Sensitivity and Specificity
16.
Acta Radiol ; 49(4): 475-83, 2008 May.
Article in English | MEDLINE | ID: mdl-18415795

ABSTRACT

BACKGROUND: Dose reduction is crucial in pediatric multidetector computed tomography (MDCT). PURPOSE: To perform pediatric 16-slice MDCT using tube current modulations and to adjust prospectively the tube current using a patient image gallery (IG) providing simulated dose-reduced protocols; and to evaluate and compare the image quality of the IG and the clinical MDCT. MATERIAL AND METHODS: 30 examinations (thorax, n = 15; abdomen, n = 8; pelvis, n = 7) in 20 patients (nine male, age 8.05 +/- 7.33 years, weight 29.8 +/- 24.02 kg) were performed according to an IG on a 16-slice MDCT with additional use of online tube current modulation (CARE Dose). Three radiologists visually assessed image quality from the IG and actual 16-slice MDCT scans. For objective analysis, image noise was determined. RESULTS: Statistical analysis showed moderate concordance in objective (K = 0.68-0.78) and subjective (K = 0.33-0.64) image assessment between the IG and clinical 16-slice MDCT scans. Depending on the weight group and clinical question, no or only minor dose reductions in the chest, but moderate to considerable reductions in the abdominal/pelvic 16-slice MDCT scans compared to previously used pediatric protocols were achieved. Extra dose reduction was achieved due to additional use of CARE Dose depending on age group and scan region (mean 8.6-23.9%). CONCLUSION: The IG enabled us to prospectively reduce the tube current and adapt the required image quality to the clinical question. Additional dose reduction was achieved with application of CARE Dose; nevertheless, the images are comparable to the simulated images of the IG.


Subject(s)
Tomography, X-Ray Computed/methods , Artifacts , Child , Computer Simulation , Female , Humans , Male , Poisson Distribution , Prospective Studies , Radiation Injuries/prevention & control
17.
Clin Microbiol Infect ; 13(12): 1173-8, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17850344

ABSTRACT

A nationwide voluntary laboratory-based surveillance study of invasive Streptococcus pyogenes (group A streptococcus; GAS) infections was conducted in Germany between 1996 and 2002. Demographical and clinical information concerning the patients was obtained from the medical files. Multiple logistic regression analysis was used to determine risk-factors for fatal outcome. Invasive isolates were obtained from 475 patients, with 251 (52.8%) of the isolates cultured from blood. The most frequent emm types were emm1 (36.4%), emm28 (8.8%) and emm3 (8%). The speA, speC and ssa genes were present at variable frequencies in different emm types. The highest frequencies of speA and speC were found in emm1 (speA, 93.6%) and emm4 (speC, 94.7%), respectively. The estimated annual incidence of invasive GAS disease for 1997-2002 was 0.1 cases/100 000 individuals. This apparently low incidence rate might be explained by the voluntary nature of the surveillance system, resulting in relatively few cases being referred to the laboratory. Complete clinical information was available for 165 cases. The overall case fatality rate was 40.6%, and was highest (65.2%) in the group aged 60-69 years. Shock, an age of >or=30 years and adult respiratory distress syndrome were predictors of a fatal outcome in a multiple logistic regression analysis. Overall, 6.7% of the cases were considered to be nosocomial, and nine cases of puerperal sepsis were observed. The study underscores the importance of invasive S. pyogenes disease in Germany.


Subject(s)
Streptococcal Infections/epidemiology , Streptococcal Infections/microbiology , Streptococcus pyogenes/classification , Streptococcus pyogenes/isolation & purification , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Antigens, Bacterial/genetics , Bacterial Outer Membrane Proteins/genetics , Bacterial Proteins/genetics , Carrier Proteins/genetics , Child , Child, Preschool , Community-Acquired Infections/microbiology , Cross Infection/microbiology , Exotoxins/genetics , Female , Germany/epidemiology , Humans , Incidence , Infant , Infant, Newborn , Logistic Models , Male , Membrane Proteins/genetics , Middle Aged , Risk Factors , Streptococcal Infections/mortality , Streptococcus pyogenes/genetics
18.
Z Orthop Unfall ; 145(2): 139-45, 2007.
Article in German | MEDLINE | ID: mdl-17492551

ABSTRACT

AIM: Here we present first clinical results of the treatment of patellofemoral cartilage lesions with a 3D collagen gel (CaReS). METHODS: Isolated patellofemoral cartilage lesions in 14 patients (13 patellar, 1 trochlear) were treated by matrix-based ACT using a collagen gel seeded with autologous chondrocytes. In this study, only those patients were taken into account who complied with the inclusion criteria of the German working group "tissue regeneration and tissue substitutes". Data were analysed in accordance with the ICRS criteria and the Brittberg score. We present the 2-year postoperative clinical follow-up. RESULTS: After 2 years the ICRS-IKDC and Brittberg scores revealed a statistically significant improvement. The preoperative rating of the objectiveIKDC and functional ICRS score improved from 0/14 and 2/14 (14.3%) to 11/14 (78.6%) in the categories A/B and I/II, respectively. 11 Patients(78.6%) judged the clinical outcome as excellent or good. The subjective IKDC score improved from 32.4 +/- 8.4 prior to operation to 67.8 +/- 27.4 at the 2-years follow-up. CONCLUSION: The use of 3D matrix systems could represent a promising improvement of conventional ACT in the treatment of patellofemoral cartilage lesions, but the results have to be verified by long-term investigations.


Subject(s)
Chondrocytes/transplantation , Collagen/therapeutic use , Fractures, Cartilage/surgery , Knee Injuries/surgery , Tissue Engineering/methods , Adolescent , Adult , Biocompatible Materials/therapeutic use , Cell Culture Techniques/instrumentation , Cell Culture Techniques/methods , Cells, Cultured , Female , Gels/therapeutic use , Humans , Longitudinal Studies , Male , Pilot Projects , Treatment Outcome
20.
Acta Radiol ; 47(1): 36-42, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16498931

ABSTRACT

PURPOSE: To compare the use of a new 64-slice computed tomography (CT) scanner with 16-slice CT in the visualization of coronary artery stent lumen. MATERIAL AND METHODS: Eight different coronary artery stents, each with a diameter of 3 mm, were placed in a static chest phantom. The phantom was positioned in the CT gantry at an angle of 0 degrees and 45 degrees towards the z-axis and examined with both a 64-slice and a 16-slice CT scanner. Effective slice thickness was 0.6 mm with 64-slice CT and 1 mm with 16-slice CT. A reconstruction increment of 0.3 mm was applied in both scanners. Image quality was assessed visually using a 5-point grading scale. Stent diameters were measured and compared using paired Wilcoxon tests. RESULTS: Artificial lumen reduction was significantly less with 64-slice than with 16-slice CT. Average visible stent lumen was 53.4% using 64-slice CT and 47.5% with 16-slice MSCT. Most severe artifacts were seen in stents with radiopaque markers. Using 64-slice CT, image noise increased by approximately 30% due to thinner slice thickness. CONCLUSION: Improved spatial resolution of 64-slice CT resulted in superior assessment of coronary artery stent lumen compared to 16-slice CT. However, a relevant part of the stent lumen is still not assessable with multi-slice CT.


Subject(s)
Coronary Angiography/instrumentation , Coronary Angiography/methods , Phantoms, Imaging , Stents , Tomography, X-Ray Computed/instrumentation , Tomography, X-Ray Computed/methods , Artifacts , Coronary Stenosis/diagnosis , Graft Occlusion, Vascular/diagnosis , Observer Variation , Reproducibility of Results
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