The effects of maternal hypercapnia on foetal oxygenation and uterine blood flow in the pig.

1. The purpose of this investigation was to determine the effects of maternal hyperoxaemia and hypercapnia on the uterine vascular bed and foetal oxygenation in the large white sow at 80-90 days gestation. 2. When maternal hyperoxaemia was induced with 100% oxygen, there was a highly significant rise in the maternal arterial oxygen tension, but no other significant blood gas or vascular changes were observed. 3. When mild maternal hypercapnia was superimposed on maternal hyperoxaemia (oxygen plus 6% carbon dioxide), the oxygen tension and saturation of both the maternal uterine venous and foetal umbilical venous bloods were found when severe hypercapnia was induced (oxygen plus 50% carbon dioxide) but in this case all blood samples showed dramatic changes in PCO2 and pH. These changes were accompanied by an increase in the systemic blood pressure and uterine blood flow, and a decrease in uterine vascular resistance. 4. When mild hypercapnia was induced without hyperoxaemia (air plus 5% carbon dioxide) significant increases were recorded in the oxygen tension and saturation of uterine venous and foetal umbilical venous bloods. Systemic and uterine vascular resistance fell. 5. It was concluded that the increased foetal oxygen tension during maternal hypercapnia was the result of the increased uterine blood flow and greater mass delivery of oxygen to the placenta, so that once the oxygen requirements of the placental tissues themselves were exceeded there would be an increased oxygen gradient at the site of gas exchange. 6. Carbon dioxide concentration in arterial blood plays an important role in determining blood flow through the pregnant uterus in the sow.     

SMAD2 Mutations Are Associated with Arterial Aneurysms and Dissections

We report three families with arterial aneurysms and dissections in which variants predicted to be pathogenic were identified in SMAD2. Moreover, one variant occurred de novo in a proband with unaffected parents. SMAD2 is a strong candidate gene for arterial aneurysms and dissections given its role in the TGF‐β signaling pathway. Furthermore, although SMAD2 and SMAD3 probably have functionally distinct roles in cell signaling, they are structurally very similar. Our findings indicate that SMAD2 mutations are associated with arterial aneurysms and dissections and are in accordance with the observation that patients with pathogenic variants in genes encoding proteins involved in the TGF‐β signaling pathway exhibit arterial aneurysms and dissections as key features     

Effect of single doses of SLV306, an inhibitor of both neutral endopeptidase and endothelin-converting enzyme, on pulmonary pressures in congestive heart failure

SLV306, a potent neutral endopeptidase (NEP) inhibitor with additional endothelin-converting enzyme (ECE)-inhibitory activity, in doses of 200, 400, and 800 mg reduced pulmonary and right atrial pressures, although there was not a clear dose response. Systemic blood pressure, heart rate, and cardiac output were unaffected. SLV306 increased plasma natriuretic peptides and big endothelin-1 levels in a dose-dependent manner, confirming NEP and ECE inhibition. The combined inhibition of NEP and ECE may be useful in heart failure by reducing right and left cardiac filling pressures.     

Worldwide Experience with the Robotic Navigation System in Catheter Ablation of Atrial Fibrillation: Methodology, Efficacy and Safety

Worldwide Survey on Robotic AF Ablation . Introduction: The Hansen Robotic system has been utilized in ablation procedures for atrial fibrillation (AF). However, because of the lack of tactile feedback and the rigidity of the robotic sheath, this approach could result in higher risk of complications. This worldwide survey reports a multicenter experience on the methodology, efficacy, and safety of the Hansen system in AF ablations. Methods and Results: A questionnaire addressing questions on patient's demographics, procedural parameters, ablation success rate and safety information was sent to all centers where more than 50 robotic AF ablation cases have been performed. From June 2007 to December 2009, 1,728 procedures were performed at 12 centers utilizing the Hansen robotic navigation technology. The overall complication rate was 4.7% and the success rate was 67.1% after 18 ± 4 months of follow‐up. In 5 low volume centers there appeared to be a learning curve of about 50 cases (complication rate 11.2% for the first 50 cases vs 3.7% for the 51–100 cases; P = 0.044) and a trend showing a decrease of complication rate with increasing case volume. However, in the remaining 7 centers no learning curve was present and the complication rate was stable over time (3.7% for the first 50 cases vs 3.6% for the 51st case thereafter; P = 0.942). Conclusion: The Hansen robotic system can be used for AF ablation safely. In low volume centers, there appeared to be a learning curve of the first 50 cases after which the complication rate decreased. With a higher case volume, the success rate increased. (J Cardiovasc Electrophysiol, Vol. 23, pp. 820‐826, August 2012)     

Development of a TLD mailed system for remote dosimetry audit for (192)Ir HDR and PDR sources.

BACKGROUND AND PURPOSE: In the framework of an ESTRO ESQUIRE project, the BRAPHYQS Physics Network and the EQUAL-ESTRO laboratory have developed a procedure for checking the absorbed dose to water in the vicinity of HDR or PDR sources using a mailed TLD system. The methodology and the materials used in the procedure are based on the existing EQUAL-ESTRO external radiotherapy dose checks. MATERIALS AND METHODS: A phantom for TLD postal dose assurance service, adapted to accept catheters from different HDR afterloaders, has been developed. The phantom consists of three PMMA tubes supporting catheters placed at 120 degrees around a central TLD holder. A study on the use of LiF powder type DTL 937 (Philitech) has been performed in order to establish the TLD calibration in dose-to-water at a given distance from (192)Ir source, as well as to determine all correction factors to convert the TLD reading into absorbed dose to water. The dosimetric audit is based on the comparison between the dose to water measured with the TL dosimeter and the dose calculated by the clinical TPS. Results of the audits are classified in four different levels depending on the ratio of the measured dose to the stated dose. The total uncertainty budget in the measurement of the absorbed dose to water using TLD near an (192)Ir HDR source, including TLD reading, correction factors and TLD calibration coefficient, is determined as 3.27% (1s). RESULTS: To validate the procedures, the external audit was first tested among the members of the BRAPHYQS Network. Since November 2004, the test has been made available for use by all European brachytherapy centres. To date, 11 centres have participated in the checks and the results obtained are very encouraging. Nevertheless, one error detected has shown the usefulness of this audit. CONCLUSION: A method of absorbed dose to water determination in the vicinity of an (192)Ir brachytherapy source was developed for the purpose of a mailed TL dosimetry system. The accuracy of the procedure was determined. This method allows a check of the whole dosimetry chain for this type of brachytherapy afterloading system and can easily be performed by mail to any institution in the European area and elsewhere. Such an external audit can be an efficient QC method complementary to internal quality control as it can reveal some errors which are not observable by other means.     

The determination of phantom and collimator scatter components of the output of megavoltage photon beams: measurement of the collimator scatter part with a beam-coaxial narrow cylindrical phantom

The separation of the total scatter correction factor S_{c, p} in a collimator scatter component, S_c, and a phantom scatter component, S_p, has proven to be an useful concept in megavoltage photon beam dose calculations in situations which differ from the standard treatment geometry. A clinically applicable method to determine S_c is described. Measurements are carried out with an ionization chamber, placed at a depth beyond the range of contaminant electrons, in a narrow cylindrical polystyrene phantom with a diameter of 4 cm of which the axis coincides with the beam axis. S_{c, p} is measured in a full-scatter phantom and S_p can be derived from S_{c, p} and S_c. In order to obtain a reliable separation, i.e. excluding the influence of contaminant electrons, measurements of S_{c, p} have been carried out at depths of 5 cm for photon beams with a quality index (QI) up to and including 0.75 and a depth of 10 cm with QI larger than 0.75. These depths are in accordance with recommendations given in recent dosimetry protocols. The consistency of the method was checked by comparing calculated and measured values of S_{c, p} for a set of blocked fields for a range of photon beam energies from ⁶⁰Co up to 25 MV showing a maximum deviation of 2%. The method can easily be implemented in existing procedures for the calculation of the number of monitor units to deliver a specified dose to a target volume.     

Intracardiac echo-guided image integration: optimizing strategies for registration

Introduction: Image integration is being used in ablation procedures. However, the success of this approach is dependent on the accuracy of the image integration process. This study aims to evaluate the in vivo accuracy and reliability of the integrated image.
Methods and Results: One hundred twenty-four patients undergoing radiofrequency (RF) ablation catheter ablation for atrial fibrillation (AF) were recruited for this study from three different centers. Cardiac computerized tomography (CT) was performed in all patients and a 3D image of the left atrium (LA) and pulmonary veins (PVs) was extracted for registration after segmentation using a software program (CartoMerge, Biosense Webster, Inc.). Different landmarks were selected for registration and compared. Surface registration was then done and the impact on integration and the landmarks was evaluated.
The best landmark registration was achieved when the posterior points on the pulmonary veins were selected (5.6 ± 3.2). Landmarks taken on the anterior wall, left atrial appendage (LAA) or the coronary sinus (CS) resulted in a larger registration error (9.1 ± 2.5). The mean error for surface registration was 2.17 ± 1.65. However, surface registration resulted in shifting of the initially registered landmark points leading to a larger error (from 5.6 ± 3.2 to 9.2 ± 2.1; 95% CI 4.2–3.05).
Conclusion: Posterior wall landmarks at the PV-LA junction are the most accurate landmarks for image integration in respect to the target ablation area. The concurrent use of the present surface registration algorithm may result in shifting of the initial landmarks with loss of their initial correlation with the area of interest.