Skip to main content
eScholarship
Open Access Publications from the University of California

Scholarly Works (4 results)

  • Thesis
  • Peer Reviewed
UC San Diego Electronic Theses and Dissertations (2010)
Cardiac resynchronization therapy (CRT) is an effective intervention for patients with heart failure but has a 30% non-responder rate due to a lack of predictive, mechanism- based objective criteria for patient selection. In order to fully optimize treatment outcomes, computational models can be used to predict molecular, biomechanical, and electrophysiological mechanisms of cardiac function. The methods presented in this thesis provide an efficient technique to estimate epicardial activation time parameters and thus will prove useful as the electrophysiological input for predictive patient-specific computational model development. By developing three- dimensional isochronal maps, the sequence of ventricular activation in normal hearts, hearts with heart failure, hearts with myocardial infarcts, and hearts with ventricular dyssynchrony, such as left bundle branch block (LBBB), can be visualized. Through the use of a 128- electrode sock array, it is confirmed that the local activation time is most efficiently calculated using the time of the maximum negative derivative averaged over multiple beats. Automatic determination of the activation times proved to be comparable to manual determination (the standard). It is also seen that filtering signals causes data loss and should be avoided if possible. The calculated activation times are then input into an anatomical fit geometry of the heart to create an epicardial isochronal activation map in Continuity. Inspection of these maps reveals that endocardial pacing does not always restore more ventricular synchrony when compared to epicardial pacing, specifically in the presence of tachycardia-induced heart failure and a myocardial infarct
    Cover page: The effects of pacing location on regional activation using epicardial electrical mapping
    • Article
    UCR Honors Capstones 2020-2021 (2021)
      Cover page: Urea Cycle Review Using a Case Study on Ornithine Transcarbamylase Deficiency
      • Article
      • Peer Reviewed
      Western Journal of Emergency Medicine: Integrating Emergency Care with Population Health, Volume 19, Issue 2 (2018)

      Introduction: Atrial fibrillation (AF) is a common diagnosis of patients presenting to the emergency department (ED). Intravenous (IV) diltiazem bolus is often the initial drug of choice for acute management of AF with rapid ventricular response (RVR). The route of diltiazem after the initial IV loading dose may influence the disposition of the patient from the ED. However, no studies exist comparing oral (PO) immediate release and IV continuous infusion diltiazem in the emergency setting. The objective of this study was to compare the incidence of treatment failure, defined as a heart rate (HR) of >110 beats/min at four hours or conversion to another agent, between PO immediate release and IV continuous infusion diltiazem after an initial IV diltiazem loading dose in patients in AF with RVR.

      Methods: This was a single-center, observational, retrospective study conducted at a tertiary academic medical center. The study population included patients ≥18 years old who presented to the ED in AF with a HR > 110 beats/min and received an initial IV diltiazem loading dose. We used multivariate logistic regression to assess the association between routes of administration and treatment failure.

      Results: A total of 111 patients were included in this study. Twenty-seven percent (11/41) of the patients in the PO immediate-release group had treatment failure compared to 46% (32/70) in the IV continuous-infusion group. The unadjusted odds ratio (OR) of treatment failure with PO was less than IV at 0.4 (95% confidence interval [CI] [0.18, 0.99], p = 0.046). When we performed a multivariate analysis adjusted for race and initial HR, PO was still less likely to be associated with treatment failure than IV with an OR of 0.4 (95% CI [0.15, 0.94], p = 0.041). The median dose of PO diltiazem and IV continuous infusion diltiazem at four hours was 30 mg and 10 mg/h, respectively.

      Conclusion: After a loading dose of IV diltiazem, PO immediate-release diltiazem was associated with a lower rate of treatment failure at four hours than IV continuous infusion in patients with AF with RVR.

        Cover page: Intravenous Continuous Infusion vs. Oral Immediate-release Diltiazem for Acute Heart Rate ControlCreative Commons 'BY' version 4.0 license
        • Article
        • Peer Reviewed
        UC San Diego Previously Published Works (2010)
        Monoclonal antibodies (mAb) are an important and growing class of cancer therapeutics, but pharmacokinetic analyses have in many cases been constrained by the lack of standard and robust pharmacologic assays. The goal of this project was to develop a general method for the production of immunoassays that can measure the levels of therapeutic monoclonal antibodies in biologic samples at relevant concentrations. Alemtuzumab and rituximab are monoclonal approved for the treatment of B-cell malignancies and were used as a model system. Phage-displayed peptide libraries were screened for peptide sequences recognized by alemtuzumab (anti-CD52) or rituximab (anti-CD20). Synthetic biotinylated peptides were used in enzyme-linked immunosorbent assays (ELISA). Peptides directly synthesized on polymer resin beads were used in an immunofluorescent-based assay. Peptide mimetope sequences were recovered for both mAb and confirmed by competitive staining and kinetic measurements. A peptide-based ELISA method was developed for each. The assay for rituximab had a limit of detection of 4 μg/ml, and the assay for alemtuzumab had a limit of detection of 1 μg/ml. Antibody-specific staining of peptide conjugated beads could be seen in a dose-dependent manner. Phage-displayed peptide libraries can be a source of highly specific mimetopes for therapeutic mAb. The biotinylated forms of those peptides are compatible with conventional ELISA methods with sensitivities comparable to other assay methods and sufficient for pharmacological studies of those mAb given at high dose. The process outlined here can be applied to any mAb to enable improved pharmacokinetic analysis during the development and clinical use of this class of therapies.
          Cover page: A general process for the development of peptide-based immunoassays for monoclonal antibodies
          Top