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1.
Toxicology ; 506: 153835, 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38857863

ABSTRACT

Next Generation Risk Assessment (NGRA) is an exposure-led approach to safety assessment that uses New Approach Methodologies (NAMs). Application of NGRA has been largely restricted to assessments of consumer use of cosmetics and is not currently implemented in occupational safety assessments, e.g. under EU REACH. By contrast, a large proportion of regulatory worker safety assessments are underpinned by toxicological studies using experimental animals. Consequently, occupational safety assessment represents an area that would benefit from increasing application of NGRA to safety decision making. Here, a workflow for conducting NGRA under an occupational safety context was developed, which is illustrated with a case study chemical; sodium 2-hydroxyethane sulphonate (sodium isethionate or SI). Exposures were estimated using a standard occupational exposure model following a comprehensive life cycle assessment of SI and considering factory-specific data. Outputs of this model were then used to estimate internal exposures using a Physiologically Based Kinetic (PBK) model, which was constructed with SI specific Absorption, Distribution, Metabolism and Excretion (ADME) data. PBK modelling indicated a worst-case plasma maximum concentration (Cmax) of 0.8 µM across the SI life cycle. SI bioactivity was assessed in a battery of NAMs relevant to systemic, reproductive, and developmental toxicity; a cell stress panel, high throughput transcriptomics in three cell lines (HepG2, HepaRG and MCF-7 cells), pharmacological profiling and specific assays relating to developmental toxicity (Reprotracker and devTOX quickPredict). Points of Departure (PoDs) for SI ranged from 104 to 5044 µM. Cmax values obtained from PBK modelling of occupational exposures to SI were compared with PoDs from the bioactivity assays to derive Bioactivity Exposure Ratios (BERs) which demonstrated the safety for workers exposed to SI under current levels of factory specific risk management. In summary, the tiered and iterative workflow developed here represents an opportunity for integrating non animal approaches for a large subset of substances for which systemic worker safety assessment is required. Such an approach could be followed to ensure that animal testing is only conducted as a "last resort" e.g. under EU REACH.

2.
Children (Basel) ; 10(8)2023 Jul 27.
Article in English | MEDLINE | ID: mdl-37628294

ABSTRACT

(1) Background: Cerebral MRI plays a significant role in assessing the extent of brain injury in neonates with neonatal encephalopathy after perinatal asphyxia. Over the last decades, several MRI scoring systems were developed to enhance the predictive accuracy of MRI. The aim of this study was to validate the correlation of four established MRI scoring systems with cognitive long-term outcomes in cooled asphyxiated newborns. (2) Methods: Forty neonates with neonatal encephalopathy treated with therapeutic hypothermia were included in this retrospective study. The MRI scans from the second week of life were scored using four existing MRI scoring systems (Barkovich, NICHD, Rutherford, and Weeke). The patients' outcome was assessed with the Bayley Scales of Infant Development (BSID-III) at the age of 2 years. To evaluate the correlation between the MRI scoring system with the cognitive scores of BSID-III, the correlation coefficient was calculated for each scoring system. (3) Results: All four MRI scoring systems showed a significant correlation with the cognitive scores of BSID-III. The strongest correlation was found between the Weeke Score (r2 = 0.43), followed by the Rutherford score (r2 = 0.39), the NICHD score (r2 = 0.22), and the Barkovich score (r2 = 0.17). (4) Conclusion: Our study confirms previously published results in an independent cohort and indicates that the Weeke and Rutherford scores have the strongest correlation with the cognitive score of BSID-III in cooled asphyxiated newborns.

3.
Acta Paediatr ; 111(11): 2108-2114, 2022 11.
Article in English | MEDLINE | ID: mdl-35896864

ABSTRACT

AIM: We explored whether subnormal forced expiratory volume within 1 s (FEV1 ) at 5-9 years of age was lower in children born preterm who received less invasive surfactant administration (LISA) rather than surfactant via an endotracheal tube. METHODS: The multi-centre, randomised Nonintubated Surfactant Application trial enrolled 211 preterm infants born at 23-26 weeks of gestation from 13 level III neonatal intensive care units from April 2009 to March 2012. They received surfactant via LISA (n = 107) or after conventional endotracheal intubation (n = 104). The follow-up assessments were carried out by a single team blinded to the group assignments. The main outcome was FEV1 < 80% of predicted values. RESULTS: Spirometry was successful in 102/121 children. The other children died or were lost to follow-up. Median FEV1 was 93% (interquartile range 80%-113%) of predicted values in the LISA group and 86% (interquartile range 77-102%) in the control group (p = 0.685). Rates of FEV1 < 80% were 11/57 (19%) and 15/45 (33%), respectively, which was an absolute risk reduction of 14% (95% confidence interval -3.1% to 31.2%, p = 0.235). There were no differences in other outcome measures. CONCLUSION: The proportion of children aged 5-9 years with subnormal FEV1 was not significantly different between the groups.


Subject(s)
Pulmonary Surfactants , Child , Child, Preschool , Humans , Infant, Premature , Intubation, Intratracheal , Pulmonary Surfactants/administration & dosage , Spirometry
4.
J Antimicrob Chemother ; 75(8): 2291-2298, 2020 08 01.
Article in English | MEDLINE | ID: mdl-32464660

ABSTRACT

BACKGROUND: Vancomycin is an extensively used anti-infective drug in neonatal ICUs. However, exposure-toxicity relationships have not been clearly defined. OBJECTIVES: To evaluate the risk profile for hearing deficits in vancomycin-exposed very-low-birthweight infants (VLBWI). METHODS: In a large cohort study of the German Neonatal Network (GNN; n = 16 967 VLBWI) we assessed the association of vancomycin treatment and pathological hearing tests at discharge and at 5 year follow-up. We performed audits on vancomycin exposure, drug levels, dose adjustments and exposure to other ototoxic drugs in a subgroup of 1042 vancomycin-treated VLBWI. RESULTS: In the GNN cohort, 28% (n = 4739) were exposed to IV vancomycin therapy. In multivariable logistic regression analysis, vancomycin exposure proved to be independently associated with pathological hearing test at discharge (OR 1.18, 95% CI 1.03-1.34, P = 0.016). Among vancomycin-treated infants, a cumulative vancomycin dose above the upper quartile (>314 mg/kg bodyweight) was associated with pathological hearing test at discharge (OR 2.1, 95% CI 1.21-3.64, P = 0.009), whereas a vancomycin cumulative dose below the upper quartile was associated with a reduced risk of pathological tone audiometry results at 5 years of age (OR 0.29, 95% CI 0.1-0.8, P = 0.02, n = 147). CONCLUSIONS: Vancomycin exposure in VLBWI is associated with an increased, dose-dependent risk of pathological hearing test results at discharge and at 5 years of age. Prospective studies on long-term hearing impairment are needed.


Subject(s)
Ototoxicity , Vancomycin , Birth Weight , Cohort Studies , Humans , Infant , Infant, Newborn , Prospective Studies , Vancomycin/adverse effects
5.
J Med Microbiol ; 69(3): 396-401, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32125266

ABSTRACT

Introduction. Transmission of Enterobacterales in neonatal intensive care units (NICU) can cause outbreaks of colonization and invasive infections among neonates. Two clusters of nosocomial transmission of Klebsiella pneumoniae identified by MALDI-ToF mass-spectrometry were suspected at two NICUs in July and August 2016.Aim. To assess the potential transmission of K. pneumoniae among neonates.Methodology. Whole-genome sequencing (WGS) was performed of K. pneumoniae isolates obtained through targeted surveillance of patients and environmental sampling.Results. WGS data revealed that patient and environmental isolates represented two species, K. pneumoniae and K. variicola. Core-genome multi-locus sequence typing (cgMLST) of the isolates identified three separate transmission clusters, in Hospital A a cluster of K. pneumoniae isolates in 12 children and two environmental samples and a second cluster of K. variicola isolates in five children. In Hospital B a cluster of K. pneumoniae isolates from three children and five unrelated isolates of K. pneumoniae and two unrelated isolates of K. variicola were found.Conclusion. K. variicola can cause hospital outbreaks of colonization and infection similar to other Klebsiella spp.Preliminary results from this study were presented at the 27th European Congress of Clinical Microbiology and Infectious Diseases, April 22-25, 2018, Vienna, Austria.


Subject(s)
Cross Infection , Disease Outbreaks , Genome, Bacterial/genetics , Klebsiella Infections/epidemiology , Klebsiella pneumoniae/genetics , Klebsiella/genetics , Bacterial Typing Techniques , Germany/epidemiology , Humans , Infant, Newborn , Intensive Care Units, Neonatal , Klebsiella/drug effects , Klebsiella/isolation & purification , Klebsiella Infections/microbiology , Klebsiella Infections/transmission , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/isolation & purification , Multilocus Sequence Typing , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Whole Genome Sequencing
6.
Arch Dis Child Fetal Neonatal Ed ; 105(2): 190-195, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31248963

ABSTRACT

OBJECTIVE: To determine if survival rates of preterm infants receiving active perinatal care improve over time. DESIGN: The German Neonatal Network is a cohort study of preterm infants with birth weight <1500 g. All eligible infants receiving active perinatal care are registered. We analysed data of patients discharged between 2011 and 2016. SETTING: 43 German level III neonatal intensive care units (NICUs). PATIENTS: 8222 preterm infants with a gestational age between 22/0 and 28/6 weeks who received active perinatal care. INTERVENTIONS: Participating NICUs were grouped according to their specific survival rate from 2011 to 2013 to high (percentile >P75), intermediate (P25-P75) and low (

Subject(s)
Infant, Extremely Premature , Intensive Care Units, Neonatal/statistics & numerical data , Perinatal Care/methods , Perinatal Care/statistics & numerical data , Perinatal Mortality/trends , Cause of Death , Comorbidity , Female , Gestational Age , Health Status , Humans , Infant , Infant, Newborn , Infant, Very Low Birth Weight , Male , Prospective Studies , Quality Improvement , Risk Factors , Sex Factors , Tertiary Care Centers
7.
Thorac Cardiovasc Surg ; 67(S 04): e1-e10, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31675756

ABSTRACT

BACKGROUND: Even after successful aortic coarctation (CoA) repair, hypertension causes premature morbidity and mortality. The mechanisms are not clear. The aim was to evaluate elastic wall properties and aortic morphology and to correlate these results with severity of restenosis, hypertension, aortic arch geometry, noninvasive pressure gradients, and time and kind of surgical procedure. METHODS: Eighty-nine patients (17 ± 6.3 years) and 20 controls (18 ± 4.9 years) were examined using magnetic resonance imaging (MRI). In addition to contrast-enhanced MR angiography and flow measurements, CINE MRI was performed to assess the relative change of aortic cross-sectional areas at diaphragm level to calculate aortic compliance (C). RESULTS: Fifty-four percent of all patients showed hypertension (> 95th percentile), but more than half of them had no significant stenosis (defined as ≥30%). C was lower in CoA than in controls (3.30 ± 2.43 vs. 4.67 ± 2.21 [10-5 Pa-1 m-2]; p = 0.024). Significant differences in compliance were found between hyper- and normotensive patients (2.61 ± 1.60 vs. 4.11 ± 2.95; p = 0.01), and gothic and Romanesque arch geometry (2.64 ± 1.58 vs. 3.78 ± 2.81; p = 0.027). There was a good correlation between C and hypertension (r = 0.671; p < 0.01), but no correlation between C (and hypertension) and time or kind of repair, restenosis, or pressure gradients. CONCLUSION: The decreased compliance, a high rate of hypertension without restenosis, and independency of time and kind of repair confirm the hypothesis that CoA may not be limited to isthmus region but rather be a widespread (systemic) vascular anomaly at least in some of the CoA patients. Therefore, aortic compliance should be assessed in these patients to individually tailor treatment of CoA patients with restenosis and/or hypertension.


Subject(s)
Aorta/diagnostic imaging , Aortic Coarctation/diagnostic imaging , Arterial Pressure , Hypertension/diagnostic imaging , Magnetic Resonance Angiography , Magnetic Resonance Imaging, Cine , Vascular Stiffness , Adolescent , Adult , Antihypertensive Agents/therapeutic use , Aorta/abnormalities , Aorta/physiopathology , Aorta/surgery , Aortic Coarctation/complications , Aortic Coarctation/physiopathology , Aortic Coarctation/surgery , Arterial Pressure/drug effects , Child , Child, Preschool , Female , Humans , Hypertension/drug therapy , Hypertension/etiology , Hypertension/physiopathology , Male , Predictive Value of Tests , Prognosis , Prospective Studies , Risk Factors , Vascular Stiffness/drug effects , Young Adult
8.
Respiration ; 97(2): 108-118, 2019.
Article in English | MEDLINE | ID: mdl-30293066

ABSTRACT

BACKGROUND: Congenital cardiovascular malformations (CCVM) may cause infrequently airway pathologies (AP) in children and are of prognostic and therapeutic relevance. While computed tomography (CT) is considered first-line imaging modality in many centres, we started using magnetic resonance imaging (MRI) more and more in the last years to detect CCVM and AP to avoid radiation in this patient group. OBJECTIVE: The aim of this retrospective study was to determine and to compare the diagnostic accuracy of CT and MRI when used to detect CCVM and/or AP. METHODS: All patients suspected to have CCVM and/or AP and examined either by CT or MRI between 2000 and 2013 in our hospital were included. Extension and type of CCVM, as well as their relationship to esophagus, trachea or bronchi were assessed and related to findings of tracheobronchoscopy, cardiac catheterization or surgery if available. RESULTS: One hundred six patients (median [range] 4 years [2 days to 66 years]) were examined by CT (n = 27) or MRI (n = 79). In 78 patients (74%), CCVM and/or AP were found with either of the imaging methods. CCVM were found in 63 subjects. Forty-six of 63 subjects had both, CCVM and AP. The presence of CCVM was always detected correctly by CT or MRI, although both techniques had a weakness detecting atretic segments directly. AP (n = 61) were correctly diagnosed in all patients not intubated for artificial ventilation by CT (n = 17) and in all but 2 patients by MRI (39 out of 41). CONCLUSIONS: MRI is sensitive to detect CCVM associated with AP equally to CT without any radiation exposure.


Subject(s)
Heart Defects, Congenital/diagnostic imaging , Magnetic Resonance Imaging , Multidetector Computed Tomography , Vascular Ring/diagnostic imaging , Adolescent , Adult , Aged , Bronchial Diseases/diagnostic imaging , Child , Child, Preschool , Constriction, Pathologic/diagnostic imaging , Esophagus/diagnostic imaging , Female , Humans , Imaging, Three-Dimensional , Infant , Infant, Newborn , Male , Middle Aged , Retrospective Studies , Trachea/diagnostic imaging , Tracheal Stenosis/diagnostic imaging , Tracheobronchomalacia/diagnostic imaging , Young Adult
9.
J Cardiovasc Magn Reson ; 19(1): 8, 2016 Dec 05.
Article in English | MEDLINE | ID: mdl-28103933

ABSTRACT

BACKGROUND: The objective assessment of global and regional cardiac function in children has shown to be clinically relevant but is challenging to conduct. Cardiovascular magnetic resonance (CMR) has emerged as a valuable diagnostic modality especially in patients with cardiomyopathy or congenital heart disease. However, data on the normal cardiac deformation in children assessed by CMR is lacking at present. Thus, the aim of this study was to provide reference values for cardiac strain and strain rate in children and adolescents derived from CMR feature tracking (FT) measurements. METHODS: In this binational study, eighty children and adolescents (age 0.4-18.0 years, 41 male, 39 female) free from cardiac diseases from two centers underwent CMR in 1.5 T whole-body scanners in supine position. Global peak radial, circumferential and longitudinal systolic strains as well as the corresponding early peak diastolic strain rates were assessed applying FT on short axis as well as 3- and 4-chamber views of standard cine steady-state free precession images. RESULTS: The difference between genders yielded no significance for all assessed strains. Yet, all strains showed a significant parabolic relation to age and an even stronger one to body surface area (BSA). Therefore, BSA-specific reference values were determined using a polynomial regression model. The apical cardiac segments featured significant higher peak circumferential but lower peak radial systolic strains than the midventricular and basal segments (all p < 0.001). CONCLUSIONS: The assessment of cardiac deformation by CMR-FT is feasible in children. This is the first CMR study providing specific reference values for FT-derived strain and strain rate in the pediatric age range.


Subject(s)
Heart Ventricles/diagnostic imaging , Magnetic Resonance Imaging, Cine/standards , Myocardial Contraction , Ventricular Function, Left , Adolescent , Age Factors , Biomechanical Phenomena , Child , Child, Preschool , Female , Germany , Humans , Infant , Male , Netherlands , Observer Variation , Patient Positioning , Predictive Value of Tests , Reference Standards , Reproducibility of Results , Stress, Mechanical , Supine Position , Whole Body Imaging
10.
Int J Cardiovasc Imaging ; 31(4): 823-30, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25645544

ABSTRACT

To assess spatial and temporal pressure characteristics in patients with repaired aortic coarctation compared to young healthy volunteers using time-resolved velocity-encoded three-dimensional phase-contrast magnetic resonance imaging (4D flow MRI) and derived 4D pressure difference maps. After in vitro validation against invasive catheterization as gold standard, 4D flow MRI of the thoracic aorta was performed at 1.5T in 13 consecutive patients after aortic coarctation repair without recoarctation and 13 healthy volunteers. Using in-house developed processing software, 4D pressure difference maps were computed based on the Navier-Stokes equation. Pressure difference amplitudes, maximum slope of pressure amplitudes and spatial pressure range at mid systole were retrospectively measured by three readers, and twice by one reader to assess inter- and intraobserver agreement. In vitro, pressure differences derived from 4D flow MRI showed excellent agreement to invasive catheter measurements. In vivo, pressure difference amplitudes, maximum slope of pressure difference amplitudes and spatial pressure range at mid systole were significantly increased in patients compared to volunteers in the aortic arch, the proximal descending and the distal descending thoracic aorta (p < 0.05). Greatest differences occurred in the proximal descending aorta with values of the three parameters for patients versus volunteers being 19.7 ± 7.5 versus 10.0 ± 2.0 (p < 0.001), 10.9 ± 10.4 versus 1.9 ± 0.4 (p = 0.002), and 8.7 ± 6.3 versus 1.6 ± 0.9 (p < 0.001). Inter- and intraobserver agreements were excellent (p < 0.001). Noninvasive 4D pressure difference mapping derived from 4D flow MRI enables detection of altered intraluminal aortic pressures and showed significant spatial and temporal changes in patients with repaired aortic coarctation.


Subject(s)
Aorta, Thoracic/physiopathology , Aorta, Thoracic/surgery , Aortic Coarctation/surgery , Arterial Pressure , Blood Pressure Determination/methods , Cardiac Surgical Procedures/adverse effects , Magnetic Resonance Imaging/methods , Postoperative Complications/diagnosis , Adolescent , Adult , Aortic Coarctation/diagnosis , Aortic Coarctation/physiopathology , Blood Flow Velocity , Catheterization, Peripheral , Child , Child, Preschool , Female , Humans , Male , Models, Anatomic , Models, Cardiovascular , Observer Variation , Postoperative Complications/physiopathology , Predictive Value of Tests , Regional Blood Flow , Reproducibility of Results , Retrospective Studies , Signal Processing, Computer-Assisted , Software , Time Factors , Treatment Outcome , Young Adult
11.
J Pediatr Endocrinol Metab ; 27(9-10): 915-22, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24854524

ABSTRACT

AIM: The aim of this study was to evaluate the morphology and elastic properties of the aorta in children and adolescents with Ullrich-Turner syndrome (UTS) treated with growth hormone, by using magnetic resonance imaging (MRI). METHODS: Thirty-seven conscious UTS patients were examined using a 1.5-T whole-body MRI. Contrast-free three-dimensional (3D)-MR angiographies were performed, including 2D cine MRI, to calculate the aortic compliance (C) and cine of the aortic valve. RESULTS: Changes of aortic morphology were evident in 40% of the patients, whereas six had more than one alteration. A bicuspid aortic valve was identified in three patients that were missed by previous echocardiography. The aortic compliances in UTS patients were similar to those in healthy persons. CONCLUSION: This study shows that aortic morphology and compliance can be assessed by MRI without using contrast agents and without sedation in children and adolescents with UTS.


Subject(s)
Aorta/pathology , Magnetic Resonance Imaging , Turner Syndrome/pathology , Adolescent , Aortography , Child , Cross-Sectional Studies , Female , Humans , Male , Prospective Studies , Turner Syndrome/diagnostic imaging
12.
Cardiovasc Diagn Ther ; 4(2): 97-103, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24834408

ABSTRACT

PURPOSE: To develop a method for computing and visualizing pressure differences derived from time-resolved velocity-encoded three-dimensional phase-contrast magnetic resonance imaging (4D flow MRI) and to compare pressure difference maps of patients with unrepaired and repaired aortic coarctation to young healthy volunteers. METHODS: 4D flow MRI data of four patients with aortic coarctation either before or after repair (mean age 17 years, age range 3-28, one female, three males) and four young healthy volunteers without history of cardiovascular disease (mean age 24 years, age range 20-27, one female, three males) was acquired using a 1.5-T clinical MR scanner. Image analysis was performed with in-house developed image processing software. Relative pressures were computed based on the Navier-Stokes equation. RESULTS: A standardized method for intuitive visualization of pressure difference maps was developed and successfully applied to all included patients and volunteers. Young healthy volunteers exhibited smooth and regular distribution of relative pressures in the thoracic aorta at mid systole with very similar distribution in all analyzed volunteers. Patients demonstrated disturbed pressures compared to volunteers. Changes included a pressure drop at the aortic isthmus in all patients, increased relative pressures in the aortic arch in patients with residual narrowing after repair, and increased relative pressures in the descending aorta in a patient after patch aortoplasty. CONCLUSIONS: Pressure difference maps derived from 4D flow MRI can depict alterations of spatial pressure distribution in patients with repaired and unrepaired aortic coarctation. The technique might allow identifying pathophysiological conditions underlying complications after aortic coarctation repair.

13.
A A Case Rep ; 1(1): 5-7, 2013 Oct.
Article in English | MEDLINE | ID: mdl-25611601

ABSTRACT

Patients with glutaric aciduria type I are at risk for acute striatal injury precipitated by catabolic stress. Here, we report the successful interdisciplinary anesthetic and perioperative management of a child with glutaric aciduria type I undergoing cardiac surgery with extracorporeal circulation. Given the central focus on prevention of acute striatal injury, our anesthetic strategy emphasized avoiding a high protein load, high-dose inotropics, especially epinephrine (associated with impaired glucose utilization), deliberate hyperventilation, and other interventions associated with systemic inflammatory response.

15.
Catheter Cardiovasc Interv ; 72(4): 544-51, 2008 Oct 01.
Article in English | MEDLINE | ID: mdl-18814228

ABSTRACT

OBJECTIVE: To evaluate varying CT settings to visualize pediatric vascular stents in comparison to digital angiography (DA). BACKGROUND: There is a great clinical interest in substituting noninvasive methods to follow up children with congenital heart disease after interventional treatment. MATERIALS AND METHODS: CT studies in small children with transcatheter placed stents were reviewed, retrospectively. Furthermore, eight stents were implanted in tubes and partially obstructed. CT exams were performed on varying scanners (4 up to 64 slices) with corresponding tube settings. The effects of dose on image quality were evaluated regarding stent size, strut thickness, and in-stent stenoses in comparison to DA. RESULTS: Fourteen children with 28 implanted stents were identified. Significant differences between higher and lower radiation settings were not found, corresponding with the phantom, where moderate tube setting showed the best results. In vitro, there was an improvement with increasing number of detector rows, which resulted in a decrease of stent strut overestimation (295% down to 201%; P < 0.0001) and a better agreement with DA measurements for mild (78% up to 91%; P = 0.003) and moderate in-stent stenoses (80% up to 99%; P = 0.0001). CONCLUSION: Higher radiation exposure settings did not improve image quality, suggesting that the exams could be performed at a lower radiation dose.


Subject(s)
Angiography, Digital Subtraction , Cardiac Catheterization/instrumentation , Coronary Angiography/methods , Graft Occlusion, Vascular/diagnostic imaging , Heart Defects, Congenital/therapy , Radiography, Interventional/methods , Stents , Tomography, X-Ray Computed , Artifacts , Cardiac Catheterization/adverse effects , Child, Preschool , Constriction, Pathologic , Feasibility Studies , Female , Graft Occlusion, Vascular/etiology , Heart Defects, Congenital/diagnostic imaging , Humans , Infant , Male , Phantoms, Imaging , Predictive Value of Tests , Radiation Dosage , Radiographic Image Interpretation, Computer-Assisted , Retrospective Studies
16.
Echocardiography ; 25(7): 732-8, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18445060

ABSTRACT

BACKGROUND: Ventricular dysfunction represents one of the major problems in the long-term follow-up of patients after atrial repair for dextrotransposition of the great arteries. We aimed to study the role of tissue Doppler derived isovolumic acceleration (IVA) to detect early myocardial dysfunction in these patients. METHODS: Twenty-four patients with dextrotransposition of the great arteries (D-TGA) that underwent atrial repair (Senning procedure: n = 12; Mustard procedure: n = 12) in infancy were examined at the age of 21 [12-33] years (median [range]) using tissue Doppler analysis of IVA and peak systolic myocardial velocity at rest and during exercise. 12 age-matched healthy subjects served as controls. RESULTS: At rest, IVA and peak systolic myocardial velocity were reduced in the systemic ventricle (SV) of patients. IVA correlated with peak systolic myocardial velocity (r = 0.76, P < 0.001). During exercise, IVA, but not peak systolic myocardial velocity, increased significantly in the SV of patients (rest: 1.03 +/- 0.44 cm/sec(2); 1 W/kg: 1.80 +/- 1.22 cm/sec(2); 2 W/kg: 2.85 +/- 1.26 cm/sec(2)). In the subpulmonary ventricle, IVA was significantly lower in patients compared to the controls (patients: 1.45 +/- 0.49 cm/sec(2) vs. controls: 2.31 +/- 0.43 cm/sec(2), P < 0.05). IVA but not peak systolic myocardial velocity was able to discriminate between patients and healthy subjects. CONCLUSIONS: IVA is superior to peak systolic myocardial velocity to assess a reduction in functional reserve of both ventricles in patients after atrial repair for D-TGA.


Subject(s)
Cardiac Surgical Procedures/methods , Echocardiography, Doppler/methods , Heart Atria/surgery , Myocardial Contraction/physiology , Transposition of Great Vessels/diagnostic imaging , Transposition of Great Vessels/surgery , Adolescent , Adult , Age Factors , Cardiac Surgical Procedures/mortality , Case-Control Studies , Cross-Sectional Studies , Echocardiography, Doppler, Color , Female , Follow-Up Studies , Heart Atria/diagnostic imaging , Humans , Male , Reference Values , Reproducibility of Results , Risk Assessment , Sex Factors , Stroke Volume/physiology , Time Factors , Transposition of Great Vessels/mortality , Treatment Outcome , Young Adult
17.
AJR Am J Roentgenol ; 190(5): 1241-6, 2008 May.
Article in English | MEDLINE | ID: mdl-18430838

ABSTRACT

OBJECTIVE: The purpose of our study was to assess the visibility of lumen narrowing of pediatric vascular stents using various CT dose parameters in an in vitro model. MATERIALS AND METHODS: Ten steel stents of varying designs and sizes commonly used in the treatment of congenital heart disease were implanted in polyvinyl chloride (PVC) tubes and three of the 10 stents were partially obstructed with wax by filling 25% (mild) to 60% (moderate) of the lumen with contrast material. On a 64-MDCT scanner, the stents were scanned at tube voltages (kVp) of 80, 100, and 120 and at tube currents (mA) of 40, 80, 120, and 160. CT measurements of inner-stent diameter, strut thickness, and percent lumen (in-stent) stenoses were compared with biplane fluoroscopy of digital angiography. RESULTS: The stent diameter and percent stenosis on all CT images were consistently smaller than measured on digital angiography but were highly correlated (r = 0.97; p < 0.0001) with improvement as stent diameter increased (93% agreement with digital angiography for 4-mm stent, up to 99% for 25-mm stent; p = 0.001). Moderate stenosis could be assessed better than mild stenosis (99% vs 91% agreement with digital angiography; p = 0.003). Increasing exposure settings improved CT correlation of all measurements for mA up to 120 and kVp up to 100 (98.1% agreement). Higher settings did not improve accuracy (93.9% for 160 mA at 120 kVp; p = 0.03). CONCLUSION: CT is feasible to assess lumen narrowing of pediatric vascular stents at a wide range of tube settings. The study suggests that it is possible to lower the radiation exposure settings without loss in image quality or accuracy in detecting in-stent stenoses.


Subject(s)
Graft Occlusion, Vascular/diagnostic imaging , Heart Defects, Congenital/diagnostic imaging , Heart Defects, Congenital/surgery , Stents , Tomography, X-Ray Computed , Artifacts , Blood Vessel Prosthesis Implantation , Child , Coronary Angiography , Equipment Design , Humans , Models, Cardiovascular
18.
Clin Res Cardiol ; 97(6): 383-8, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18297323

ABSTRACT

BACKGROUND: Endothelin-1 (ET-1) is an endogenous vasoconstrictive peptide hormone and asymmetric dimethylarginine (ADMA) acts as an endogenous inhibitor of nitric oxide synthase. We hypothesized that both could contribute to pulmonary hypertension in patients with left-to-right shunt after intracardiac repair. PATIENTS AND METHODS: We prospectively analyzed ET-1 and ADMA plasma levels in 31 patients (m = 16; f = 15) at an age of 0.6 [0.2-27] years (median [range]) with left-to-right shunt (ASD II: n = 12; VSD: n = 11; AVSD: n = 8) presenting with a Qp/Qs of 2.7 [1.4-6.3] and a pulmonary arterial mean pressure (PAP) of 23 [13-57] mmHg. Blood specimens were taken prior to cardiopulmonary bypass (CPB), after weaning from CPB and at 3, 6, 12 and 24 h after CPB. RESULTS: 12/31 patients were found to have pulmonary hypertension prior to intracardiac repair and 11/12 patients showed persistent pulmonary hypertension during the first 24 h after CPB. Patients with pulmonary hypertension at 12 h after CPB showed significant higher plasma ET-1 compared with patients with normal PAP (1.4 [0-7.9] versus 0.5 [0-2.5] pg/ml; P = 0.048 (Mann-Whitney)). Plasma ADMA decreased from 1.3 [0.75-2.3] micromol/l before CPB to 0.7 [0.4-2.1] micromol/l at 12 h (P < 0.05). However patients with pulmonary hypertension did not show different ADMA plasma levels. CONCLUSIONS: Increased plasma ET-1 but not inhibition of nitric oxide synthase by ADMA is associated with pulmonary hypertension after intracardiac repair.


Subject(s)
Arginine/analogs & derivatives , Cardiopulmonary Bypass , Endothelin-1/blood , Hypertension, Pulmonary/blood , Postoperative Complications/blood , Adolescent , Adult , Arginine/blood , Biomarkers/blood , Child , Child, Preschool , Female , Humans , Infant , Male , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase/blood , Pancreatitis-Associated Proteins , Prospective Studies , Statistics, Nonparametric , Time Factors , Treatment Outcome , Young Adult
19.
Pediatr Radiol ; 37(10): 998-1006, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17768616

ABSTRACT

BACKGROUND: After childhood Kawasaki syndrome (KS) the coronary arteries undergo a lifelong dynamic pathological change, and follow-up coronary artery imaging is essential. At present, conventional coronary catheterization (CCC) and angiography is still regarded as the gold standard. Less-invasive methods such as multidetector CT angiography (MDCT-A) and MRI have been used sporadically. OBJECTIVE: To compare the diagnostic quality of MDCT-A and MRI with that of CCC for coronary imaging in a group of patients with coronary artery pathology after childhood KS. MATERIALS AND METHODS: A total of 16 patients (aged 5-27 years) underwent CCC and 16-row MDCT-A and 14 patients MRI (1.5 T). RESULTS: There was 100% agreement between MDCT-A and CCC in the detection of coronary aneurysms and stenoses. MDCT-A was superior for the visualization of calcified lesions. MRI and CCC showed 93% agreement for the detection of aneurysms. Visualization of coronary artery stenoses was difficult using MRI-one stenosis was missed. CONCLUSION: MDCT-A has excellent correlation with CCC regarding all changes affecting the coronary arteries in the follow-up of childhood KS. In comparison to MDCT-A and CCC, MRI is less precise in the detection of stenotic lesions. Due to its high image quality and ease of performance MDCT-A should be the primary diagnostic modality in patients following childhood KS.


Subject(s)
Cardiac Catheterization/methods , Coronary Angiography/methods , Coronary Artery Disease/diagnosis , Coronary Vessels/pathology , Magnetic Resonance Imaging/methods , Mucocutaneous Lymph Node Syndrome/diagnosis , Tomography, X-Ray Computed/methods , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Image Enhancement/instrumentation , Image Enhancement/methods , Male , Reproducibility of Results , Sensitivity and Specificity , Tomography, X-Ray Computed/instrumentation
20.
Pediatr Radiol ; 37(5): 426-36, 2007 May.
Article in English | MEDLINE | ID: mdl-17387466

ABSTRACT

BACKGROUND: Evaluation of the severity and the follow-up of aortic insufficiency (AI) are important tasks in paediatric cardiology. Assessment is based on clinical and echocardiographic (ECHO) findings such as the configuration of the valve and the regurgitation fraction (RF). OBJECTIVE: The goal of this study was to evaluate MRI compared to ECHO for determination of clinical severity, valve morphology and RF. MATERIALS AND METHODS: Thirty patients (age 3-27 years) with mild-to-severe AI were evaluated by clinical examination, ECHO (2-D and Doppler), and MRI at 1.5 T (2-D true-FISP cine short axis, phase-contrast flow in the ascending aorta). RESULTS: Both methods identified 13 bicuspid and 17 tricuspid valves. Good correlations between ECHO and cine MRI were found for ventricular mass, stroke volume, and ejection fraction. A good linear correlation was found for the RF determined by ECHO and phase-contrast MRI (r = 0.7). The RF was 6% in mild AI, 17% in moderate AI, and 30% in severe AI. The different severity groups showed significantly different RF and it was possible to discriminate between clinical severity grades (P = 0.01). CONCLUSION: ECHO and MRI showed good agreement in evaluating morphology and function of the left ventricle. The clinical severity of the disease can be evaluated correctly using MRI.


Subject(s)
Aortic Valve Insufficiency/diagnosis , Echocardiography, Doppler/methods , Heart Defects, Congenital/complications , Magnetic Resonance Imaging/methods , Adolescent , Adult , Aortic Valve/diagnostic imaging , Aortic Valve/pathology , Aortic Valve/physiopathology , Aortic Valve Insufficiency/complications , Child , Child, Preschool , Electrocardiography , Female , Follow-Up Studies , Humans , Male , Observer Variation , Prospective Studies , Severity of Illness Index , Ventricular Function, Left
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