The steroid hydroxylases CYP17A1 (P450c17, 17-hydroxylase/17,20-lyase) and CYP21A2 (P450c21, 21-hydroxylase) catalyze progesterone hydroxylation at one or more sites within a 2 Å radius. We probed their hydrogen atom abstraction mechanisms and regiochemical plasticity with deuterium-labeled substrates: 17-[2H]-pregnenolone; 17-[2H]-, 16α-[2H]-, 21,21,21-[2H3]-, and 21-[2H]-progesterone; and 21,21,21-[2H3]-17-hydroxyprogesterone. Product distribution and formation rates with recombinant human P450-oxidoreductase and wild-type human CYP17A1 or mutation A105L (reduced progesterone 16α-hydroxylation) and wild-type human CYP21A2 or mutation V359A (substantial progesterone 16α-hydroxylation) were used to calculate intramolecular and intermolecular kinetic isotope effects (KIEs). The intramolecular KIEs for CYP17A1 and mutation A105L were 4.1 and 3.8, respectively, at H-17 and 2.9 and 5.1, respectively, at H-16α. Mutation A105L 21-hydroxylates progesterone (5% of products), and wild-type CYP17A1 also catalyzes a trace of 21-hydroxylation, which increases with 16α-[2H]- and 17-[2H]-progesterone. The intramolecular KIEs with CYP21A2 mutation V359A and progesterone were 6.2 and 3.8 at H-21 and H-16α, respectively. Wild-type CYP21A2 also forms a trace of 16α-hydroxyprogesterone, which increased with 21,21,21-[2H3]-progesterone substrate. Competitive intermolecular KIEs paralleled the intramolecular KIE values, with DV values of 1.4–5.1 and DV/K values of 1.8–5.1 for these reactions. CYP17A1 and CYP21A2 mutation V359A both 16α-hydroxylate 16α-[2H]-progesterone with 33–44% deuterium retention, indicating stereochemical inversion. We conclude that human CYP17A1 has progesterone 21-hydroxylase activity and human CYP21A2 has progesterone 16α-hydroxylase activity, both of which are enhanced with deuterated substrates. The transition states for C-H bond cleavage in these hydroxylation reactions are either significantly non-linear and/or asymmetric, and C-H bond breakage is partially rate-limiting for all reactions.
ObjectExperience with freehand thoracic pedicle screw placement is well described in the literature. Published techniques rely on various starting points and trajectories for each level or segment of the thoracic spine. Furthermore, few studies provide specific guidance on sagittal and axial trajectories. The goal of this study was to propose a uniform entry point and sagittal trajectory for all thoracic levels during freehand pedicle screw placement and determine the accuracy of this technique.MethodsThe authors retrospectively reviewed postoperative CT scans of 33 consecutive patients who underwent open, freehand thoracic pedicle-screw fixation using a uniform entry point and sagittal trajectory for all levels. The same entry point for each level was defined as a point 3 mm caudal to the junction of the transverse process and the lateral margin of the superior articulating process, and the sagittal trajectory was always orthogonal to the dorsal curvature of the spine at that level. The medial angulation (axial trajectory) was approximately 30° at T-1 and T-2, and 20° from T-3 to T-12. Breach was defined as greater than 25% of the screw diameter residing outside of the pedicle or vertebral body.ResultsA total of 219 thoracic pedicle screws were placed with a 96% accuracy rate. There were no medial breaches and 9 minor lateral breaches (4.1%). None of the screws had to be repositioned postoperatively, and there were no neurovascular complications associated with the breaches.ConclusionsIt is feasible to place freehand thoracic pedicle screws using a uniform entry point and sagittal trajectory for all levels. The entry point does not have to be adjusted for each level as reported in existing studies, although this technique was not tested in severe scoliotic spines. While other techniques are effective and widely used, this particular method provides more specific parameters and may be easier to learn, teach, and adopt.
BACKGROUND AND PURPOSE:Flat panel detector CT images are degraded by streak artifacts caused by radiodense implanted materials such as coils or clips. A new metal artifacts reduction prototype algorithm has been used to minimize these artifacts. The application of this new metal artifacts reduction algorithm was evaluated for flat panel detector CT imaging performed in a routine clinical setting.
A 2-year-old boy with hypoplastic left heart syndrome that required multiple cardiovascular surgeries and a heterozygous prothrombin G20210A mutation with resulting thrombophilia maintained on warfarin presented with acute right middle cerebral artery (MCA) infarction manifesting as a left hemiplegia. An MRI revealed a complete occlusion of the right M1 segment with an area of restricted diffusion in the right basal ganglia representing only a small area of acute infarction. Patchy areas of subacute infarction were also present in the right MCA territory. He underwent endovascular mechanical thrombectomy with a stent retriever. This is an account of a successful mechanical thrombectomy performed in the youngest patient reported in the English literature to date.
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