ABSTRACT
OBJECTIVE: Infrarenal aortic neck angulation is one of the most powerful predictors of endovascular aneurysm repair failure. Whereas the "gold standard" to measure this angle is three-dimensional (3D) reconstruction and centerline measurement, many surgeons rely on estimations of angulation based on two-dimensional (2D) views of computed tomography imaging. Unfortunately, these views do not accurately represent the true angle, particularly if aortic angulation is oblique to the standard views. In response to this issue, our group has developed a novel trigonometric formula that uses coronal and sagittal measured angles to calculate the true angle. The purpose of this study was to compare the paired angle formula with 3D centerline measurements for estimating true aortic neck angulation. METHODS: Fifty randomly selected patients treated by endovascular aneurysm repair at The Ottawa Hospital between 2010 and 2015 were studied. The 3D centerline aortic neck angle measurements were made by a radiology staff physician. The paired angle formula was applied by a vascular surgeon, resident, and student using 2D coronal and sagittal angles from computed tomography imaging to estimate the true angle. RESULTS: The average age was 78 years; 74% of patients were male, and average preoperative aneurysm diameter was 5.7 cm. The mean neck length was 1.9 cm (1.1-3.2 cm), and mean neck angulation calculated by the gold standard measurements was 39 degrees (2-84 degrees). Linear regression demonstrated strong association between 3D measurements and the paired angle formula, with correlations comparable to the intraobserver variability (intraclass correlation coefficient values range, 0.74-0.87). The average user estimates deviated minimally from the gold standard (absolute difference, 6 degrees; 95% confidence interval, 4-8 degrees) without systemic bias. The paired angle formula accurately ruled out severe angulation >60 degrees with an overall negative predictive value of >99%. Compared with isolated 2D measurements, application of the paired angle formula significantly decreased the false-negative rate of unappreciated severe angulation >60 degrees from 4.8% to 0.7% (P = .032). CONCLUSIONS: The paired angle formula detects significantly more severe angles than isolated 2D measurements and can accurately rule out severe angulation >60 degrees compared with the 3D measurements. The implementation of this angle estimation method is a useful adjunct in the measurement of aortic neck angulation, especially if 3D reconstruction software is not readily available. Furthermore, the importance of accurate angle measurement is not limited to vascular surgery and has direct relevance to any procedural specialty that relies on preoperative angle measurements.
Subject(s)
Aorta, Abdominal/diagnostic imaging , Aortic Aneurysm, Abdominal/diagnostic imaging , Aortography/methods , Computed Tomography Angiography , Aged , Aorta, Abdominal/surgery , Aortic Aneurysm, Abdominal/surgery , Blood Vessel Prosthesis Implantation , Databases, Factual , Endovascular Procedures , Female , Humans , Imaging, Three-Dimensional , Male , Observer Variation , Ontario , Predictive Value of Tests , Radiographic Image Interpretation, Computer-Assisted , Reproducibility of Results , Retrospective StudiesABSTRACT
An analogous library of 2-substituted quinoline compounds was synthesized with the aim to identify a potential drug candidate to treat visceral leishmaniasis. These molecules were tested for their in vitro and in vivo biological activity against Leishmania donovani. Metabolic stability of these compounds was also improved through the introduction of halogen substituents. Compound (26g), found to be the most active; exhibited an IC50 value of 0.2 µM and >180 fold selectivity. The hydrochloride salt of (26g) showed 84.26 ± 4.44 percent inhibition at 50 mg/kg × 5 days (twice daily, oral route) dose in L. donovani/hamster model. The efficacy was well correlated with the PK data observed which indicating that the compound is well distributed.
Subject(s)
Antiprotozoal Agents/pharmacology , Drug Design , Leishmania donovani/drug effects , Leishmaniasis, Visceral/drug therapy , Quinolines/pharmacology , Animals , Antiprotozoal Agents/administration & dosage , Antiprotozoal Agents/chemical synthesis , Cell Line , Cricetinae , Disease Models, Animal , Leishmaniasis, Visceral/parasitology , Macrophages/drug effects , Macrophages/parasitology , Male , Mice , Parasitic Sensitivity Tests , Quinolines/administration & dosage , Quinolines/chemical synthesisABSTRACT
A series of new 2-substituted [4-(1,3,4-oxadiazol-2-yl)methyl]phthalazin-1(2H)-one derivatives 7a-h to 9a-h were designed and synthesized from methyl (4-oxo-3,4-dihydrophthalazin-1-yl)acetate (4), which in was turn prepared from phthalic anhydride. The structure of synthesized new compounds were characterized by spectral data and screened for their antimicrobial activities against various bacteria and fungi strains. Several of these compounds showed antimicrobial activity.
