J.D. Rogers

Grapefruit juice has minimal effects on plasma concentrations of lovastatin‐derived 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors

To evaluate the effect of regular‐strength grapefruit juice, a cytochrome P4503A4 (CYP3A4) inhibitor, on the pharmacokinetics of a commonly prescribed regimen of oral lovastatin.

High-performance liquid chromatographic methods for the determination of a new carbapenem antibiotic, L-749,345, in human plasma and urine

A column-switching, reversed-phase high-performance liquid chromatographic (HPLC) method for the determination of a new carbapenem antibiotic assay using ultraviolet detection has been developed for a new carbapenem antibiotic L-749,345 in human plasma and urine. A plasma sample is centrifuged and then injected onto an extraction column using 25 mM phosphate buffer, pH 6.5. After 3 min, using a column-switching valve, the analyte is back-flushed with 10.5% methanol-phosphate buffer for 3 min onto a Hypersil 5 microm C18 BDS 100x4.6 mm analytical column and then detected by absorbance at 300 nm. The sample preparation and HPLC conditions for the urine assay are similar, except for a longer analytical column 150x4.6 mm. The plasma assay is specific and linear from 0.125 to 50 microg/ml; the urine assay is linear from 1.25 to 100 microg/ml.

Enantioselective high-performance liquid chromatographic determination of omeprazole in human plasma

A new stereoselective HPLC assay was developed to isolate omeprazole enantiomers from human plasma using C2 solid-phase extraction cartridges and an analogue was used as internal standard. Recoveries of the (+)-isomer were 83.4 and 89.7% at 100 and 250 ng/ml, respectively. Recoveries of the (-)-isomer were 78.4 and 82.8%, respectively. Recovery of the internal standard averaged 77.2%. Direct chiral separation of the enantiomers is achieved on a Resolvosil BSA-7 chiral column (15 cm x 4 mm I.D.) and a matching guard column. The mobile phase is a variable amount of n-propanol (0.05-1.0%) in 0.05 M ammonium phosphate buffer (pH 7.0) and the flow-rate is 1.5 ml/min. Drug absorbance is monitored at 302 nm. Standard curves are linear from 15 to 250 ng/ml for each enantiomer. The coefficients of variation for intra-day precision at each concentration over the range of the standard curve were between 0.98 and 10.87%. The coefficients of variation for inter-day precision for the analyses of omeprazole enantiomers in plasma (30 and 175 ng/ml) were less than 10% over a four month interval.

LC/MS/MS plasma assay for the peptidomimetic VLA4 antagonist I and its major active metabolite II: for treatment of asthma by inhalation

In vitro and in animals, I is a potent and specific peptidomimetic for the potential treatment of airway inflammation in the pathogenesis of asthma. Preclinical studies indicated extensive conversion of I to an active metabolite II, and thus, a very sensitive assay for I and II was needed to support an inhalation ascending-dose study in man. The LC/MS/MS plasma/urine assay method (1.0 ml of sample) involves the following: liquid-liquid extraction of acidified plasma into pentane-ethyl acetate (90:10 v/v); evaporation of the organic extract, reconstitution into methanol; addition of water to the methanolic extract and freezing. After thawing, the extract is centrifuged and the clear supernatant injected for chromatography. Extract is chromatographed on a YMC ODS-AM column (50 x 2.0 mm). For detection, a Sciex 365 LC/MS/MS with an electrospray inlet and used in the positive ion, multiple reaction monitoring mode was used to monitor precursor-->fragment ions of m/z 709-->594 for I and m/z 513-->380 for II. The plasma assay was linear over the concentration range of 0.1-100 ng/ml in plasma for I and II. Accuracy and precision for I ranged from 97.9 to 102.1% of nominal with a 0.84-10.65% CV; similarly for II, 98.0-101.7% and 1.39-9.28% CV, respectively. Extraction recovery averaged 63.7% for I and 64.9% for II. This general assay methodology may be applied to assay small acidic peptides and peptidomimetics from biological fluids by LC/MS/MS.

Direct-injection HPLC assay for the determination of a new carbapenem antibiotic in human plasma and urine.

Reversed-phase high-performance liquid chromatography (RP-HPLC) assays using ultraviolet (UV) absorbance detection have been developed for the determination of a new carbapenem antibiotic I in human plasma and urine. A column-switching technique is employed in the HPLC methods to perform on-line extraction and separation for each sample. Each plasma sample is thawed, centrifuged, stabilized, and then injected onto an in-line reversed-phase extraction column using a methanol (8%)/phosphate buffer, pH 6.5. After 3 min, the analytes are back-flushed off the extraction column with a mixture of acetonitrile (5.5%) and methanol (10%)/phosphate buffer (pH 6.5) for 3 min onto a BDS Hypersil 3 microm C18 (100 x 4.6 mm i.d.) analytical column. The sample preparation and HPLC conditions for the urine assay are similar to the plasma assay, except that a CN extraction column is used. Both assays are specific with respect to endogenous material and the major metabolite II, and both are linear over the concentration range of 0.25-50, and 2-200 microg/ml, respectively. The assays were successfully applied to a clinical dose-ranging study. One limitation of the on-line extraction method is that the extraction column needs to be replaced regularly every 100-150 plasma samples and every 200-300 urine samples. Subsequently, the urine method was modified to an ion-pair HPLC assay for the simultaneous determination of both the antibiotic I and its metabolite II.

Course development in interdisciplinary controls and mechatronics

As the future of engineering education emphasizes more interdisciplinary work, one logical starting point for this evolution is for faculty from different academic departments to work together. Engineering educators cannot ignore the real worldpsilas shifting focus to interdisciplinary engineering, and they should adapt as well. Similar to the total engineering process as a team effort, the engineering education process also benefits from excellent communications among a diversity of team members. This paper highlights a classical dynamical modeling and controls course with students from two different disciplines: electrical engineering and mechanical engineering. Faculties from both departments teach every semester. Sections are assigned to individual instructors but all activities are planned jointly. Course administration is the role of a course director and this role alternates between the two departments each semester. Responsibilities throughout the semester are shared between the instructors. This organizational structure is important, allowing the interdisciplinary faculty team to synchronize their efforts, each contributing their individual strengths and resources to promote student learning and faculty development. The approach is being applied to the development of a new course, Mechatronics. This paper provides details that illustrate the structure and benefits of this interdisciplinary administrative model.

Comparison of the Suture Anchor and Transosseous Techniques for Patellar Tendon Repair A Biomechanical Study

Background: Minimizing gap formation and maximizing the strength of patellar tendon repairs are 2 critical factors for successful healing of these injuries. Purpose/Hypothesis: The purpose of this study was to compare transosseous and screw-in anchor repair techniques to determine if there is a difference in gap formation and load to failure of the 2 constructs. The research hypotheses were that the anchor construct would have significantly less gap formation and would also have significantly greater load-to-failure strength. Study Design: Controlled laboratory study. Methods: A total of 24 porcine specimens were randomly assigned into transosseous and 4.75-mm polyetheretherketone (PEEK) screw-in anchor repair groups. The repairs were then completed using 2 No. 2 FiberWire sutures, and each specimen was cyclically loaded on a tensile test machine to 250 N for a total of 1000 cycles. Gap formation was measured at 1, 10, 250, 500, and 1000 cycles. Each specimen was loaded to failure after 1000 cycles. Independent t tests were conducted. Results: Statistically significant gap formation and load-to-failure differences were found between the 2 repair techniques. The mean gap in the anchor group (2.16 ± 1.81 mm) was significantly less than that seen in the transosseous group (5.71 ± 1.58 mm) (P < .001). The mean load to failure of the anchor group (669.9 ± 91.8 N) was significantly higher than that of the transosseous group (582.8 ± 92.6 N) (P = .03). Conclusion: The results support the 2 study hypotheses. These findings suggest that the 4.75-mm PEEK screw-in anchor construct may be superior to the transosseous technique for minimizing gap formation and improving load-to-failure strength after surgical repair of the patellar tendon. Clinical Relevance: The use of the suture anchor technique in patellar tendon repair may support early load-bearing rehabilitation.

Control Theory in Practice: Magnetic Levitation

A device that levitates a steel ball beneath an electromagnet is used for educational purposes at the United States Military Academy, West Point, New York. Students in the course “Mechatronics” engage in a set of laboratory exercises with the device to reinforce classroom learning. Mechatronics is a senior-level course that introduces the interdisciplinary design of smart systems. Students in the electrical engineering and mechanical engineering programs take the course together, and the material is taught by a team of instructors from both academic departments. The Magnetic Levitation experiments are the primary means of teaching the classical analog control portion of the course. Other aspects of the course involve interfacing microcontrollers with sensors and actuators, and digital control. The magnetic levitation device fits easily on a two-person workbench and requires a power supply and oscilloscope. An infra-red emitter / detector pair is used to sense ball position for a feedback compensator. Students first learn classical control theory in a co-requisite course, “Dynamic Modeling and Control.” Modeling principles are introduced in the context of the magnetic levitation system as an unstable plant to be controlled. The system can be simulated by models ranging from simply linear to more complex to teach the trade-off between model fidelity and model development effort. The students derive the nonlinear governing equations and then linearize the equations and develop the transfer function of the plant. Students design a compensator and simulate the resulting stabilized system with Matlab and Simulink software. Students build their compensator on a solderless project board to levitate the steel ball. A proven lead-type compensator using two resistors and a capacitor is readily provided to students that struggle with their own compensator design so that all teams may enjoy the fruit of a successful experiment. As a laboratory aid, the magnetic levitation system allows for basic and advanced approaches to both theoretical study and practical investigation of a nonlinear, unstable system control. The comparison of measured results to predicted behavior leads to insight about how the physical system is modeled by mathematics. Students write a case study describing the system in detail including characterization of the sensors and actuators. Instructors report that the hands-on nature motivates students to excel. Surveyed students cite the hands-on activities as relevant applications that help develop deeper understanding and greater appreciation for the concepts learned in the classroom. The students are motivated to learn by the fascination of defying gravity.

Grapefruit juice (GFJ) has a small effect on lovastatin plasma HMG‐CoA reductase inhibitor (HMGRI) profiles

Clinical Pharmacology & Therapeutics (1999) 65, 149–149; doi:

Teaching Design in Context

As a result of recent curriculum revisions, the mechanical engineering faculty at the United States Military Academy teaches the formal design process “just in time” for students to apply the process to their capstone design projects. The design process consists of several phases and incorporates many engineering tools. During the initial offering of the course, Mechanical Engineering Design, instructors assigned students to capstone design teams early in the course. As the instructor taught the design process, team members applied the concepts to their capstone project. Based on instructors’ and students’ feedback, faculty revised the course structure to teach the design process in the context of a simple, in-class design project (design a portable illumination device) during the first half-semester. All in-class exercises were collaborative, hands-on experiences based on the project. To reinforce topics introduced in class and ensure all students develop a firm foundation in the design process, a separate common customer need (a device to store a West Point class ring) was the focus of all individual homework. Each student developed a design, built a prototype, and wrote an individual design report. Subsequent to formal design process instruction, students formed capstone teams and began their one and one-half semester capstone design projects. Results indicate that students more thoroughly understood the design process and its associated engineering tools allowing capstone teams to progress more efficiently through conceptual design; order parts, build prototypes, and test prototypes much earlier than the previous year; and enjoy a successful capstone experience.