The role of lateral table tilt in obstetric anaesthesia.
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Anesthesia, Obstetrical↗
Biomedical subjects
C D Carroll
Publications and source records attributed to C D Carroll.
Evaluation of a structure-based statine cyclic diamino amide encoded combinatorial library against plasmepsin II and cathepsin D.
A structure-based 18,900-member combinatorial library was synthesized containing a statine template and three cyclic diamino acids as potential P1, P2-P4 surrogates. Evaluation of this encoded library against two aspartyl proteases, plasmepsin II and cathepsin D, led to the identification of selective inhibitors for each enzyme.
Amides↗
Identification of potent inhibitors of Plasmodium falciparum plasmepsin II from an encoded statine combinatorial library.
An encoded 13,020-member combinatorial library was synthesized containing a statine core. Evaluation of this library with plasmepsin II, an aspartyl protease required for hemoglobin metabolism in the malaria parasite, led to the identification of potent and selective inhibitors as well as novel structure-activity relationships.
Amino Acids↗
Screening aspartyl proteases with combinatorial libraries.
Large numbers of pharmaceutically relevant low-molecular weight compounds can now be synthesized using combinatorial methods. Screening these large libraries of compounds requires high throughput assays. These methods are utilized to search for inhibitors of the aspartyl proteases, plasmepsin II and cathepsin D. Plasmepsin II, a protease found in the malaria parasite, hydrolyzes human hemoglobin, the nutrient source for the parasite and is a new target for anti-malaria therapy. Cathepsin D may be involved in many biological processes and inhibitors would help to clarify the role of cathepsin D in these processes. Plasmepsin II and cathepsin D are approximately 35% identical in amino acid sequence. Therefore, a comparison of the screening results of these two enzymes will be very useful in determining each enzyme's specificity and demonstrating the power of utilizing encoded combinatorial libraries.
Animals↗
A statistical-based approach to assessing the fidelity of combinatorial libraries encoded with electrophoric molecular tags. Development and application of tag decode-assisted single bead LC/MS analysis.
A statistical sampling protocol is described to assess the fidelity of libraries encoded with molecular tags. The methodology, termed library QA, is based on the combined application of tag decode analysis and single bead LC/MS. The physical existence of library compounds eluted from beads is established by comparing the molecular weight predicted by tag decode with empirical measurement. The goal of sampling is to provide information on overall library fidelity and an indication of the performance of individual library synthons. The minimal sampling size n for library QA is l0 x the largest synthon set. Data are reported as proportion (p) +/- lower and upper boundary (lb-ub) computed at the 95% confidence level (alpha = 0.05). As a practical demonstration, library QA was performed on a 25,200-member library of statine amides (size = 40 x 63 x 10). Sampling was conducted three times at n approximately 630 beads per run for a total of 1902 beads. The overall proportions found for the three runs were consistent with one another: p = 84.4%, lb-ub = 81.5-87.2%; p = 83.1%, lb-ub = 80.2-85.95; and p = 84.5%, lb-ub = 81.8-87.3%, suggesting the true value of p is close to 84% compound confirmation. The performance pi of individual synthons was also computed. Corroboration of QA data with biological screening results obtained from assaying the library against cathepsin D and plasmepsin II is discussed.
Journal Article↗
Atlantooccipital junction: standards for measurement in normal children.
This study describes a simple method for measuring the distance between the occiput and atlas when a distraction-dislocation injury is suspected in a child. Measurements were made at five evenly spaced locations along the atlantooccipital joint on cross-table lateral skull radiographs in 100 normal children. These data were compared with similar measurements in eight patients with proved atlantooccipital dislocation. The mean normal measurement fell between 1.96-2.63 mm for all five points. For boys or girls aged 1-15 years, the normal distance should not exceed 5 mm at any point in the joint. The likelihood that any normal child will have a measurement greater than or equal to 4.5 mm at any point is between 0.4-5.85% (expected false-positive rate).
Adolescent↗