Marc D. Feldman

Thrombotic Thrombocytopenic Purpura Associated with Clopidogrel

BACKGROUNDnThe antiplatelet drug clopidogrel is a new thienopyridine derivative whose mechanism of action and chemical structure are similar to those of ticlopidine. The estimated incidence of ticlopidine-associated thrombotic thrombocytopenic purpura is 1 per 1600 to 5000 patients treated, whereas no clopidogrel-associated cases were observed among 20,000 closely monitored patients treated in phase 3 clinical trials and cohort studies. Because of the association between ticlopidine use and thrombotic thrombocytopenic purpura and other adverse effects, clopidogrel has largely replaced ticlopidine in clinical practice. More than 3 million patients have received clopidogrel. We report the clinical and laboratory findings in 11 patients in whom thrombotic thrombocytopenic purpura developed during or soon after treatment with clopidogrel.nnnMETHODSnThe 11 patients were identified by active surveillance by the medical directors of blood banks (3 patients), hematologists (6), and the manufacturer of clopidogrel (2).nnnRESULTSnTen of the 11 patients received clopidogrel for 14 days or less before the onset of thrombotic thrombocytopenic purpura. Although 10 of the 11 patients had a response to plasma exchange, 2 required 20 or more exchanges before clinical improvement occurred, and 2 had relapses while not receiving clopidogrel. One patient died despite undergoing plasma exchange soon after diagnosis.nnnCONCLUSIONSnThrombotic thrombocytopenic purpura can occur after the initiation of clopidogrel therapy, often within the first two weeks of treatment. Physicians should be aware of the possibility of this syndrome when initiating clopidogrel treatment.

Detection of magnetic nanoparticles in tissue using magneto-motive ultrasound.

The purpose of this study was to demonstrate the magneto-motive ultrasonic detection of superparamagnetic iron oxide (SPIO) nanoparticles as a marker of macrophage recruitment in tissue. The capability of ultrasound to detect SPIO nanoparticles (core diameter ∼20xa0nm) taken up by murine liver macrophages was investigated. Eight mice were sacrificed two days after the intravenous administration of four SPIO doses (1.5, 1.0, 0.5, and 0.1xa0mmol Fe/kg body weight). In the iron-laden livers, ultrasound Doppler measurements showed a frequency shift in response to an applied time-varying magnetic field. M-mode scan and colour power Doppler images of the iron-laden livers also demonstrated nanoparticle movement under focused magnetic field excitation. In the livers of two saline injected control mice, no movement was observed using any ultrasound imaging modes. The results of our experiments indicate that ultrasound imaging of magneto-motive excitation is a candidate imaging modality to identify tissue-based macrophages containing SPIO nanoparticles.

Nonlinear conductance-volume relationship for murine conductance catheter measurement system

The conductance catheter system is a tool to determine instantaneous left ventricular volume in vivo by converting measured conductance to volume. The currently adopted conductance-to-volume conversion equation was proposed by Baan, and the accuracy of this equation is limited by the assumption of a linear conductance-volume relationship. The electric field generated by a conductance catheter is nonuniform, which results in a nonlinear relationship between conductance and volume. This paper investigates this nonlinear relationship and proposes a new nonlinear conductance-to-volume conversion equation. The proposed nonlinear equation uses a single empirically determined calibration coefficient, derived from independently measured stroke volume. In vitro experiments and numerical model simulations were performed to verify and validate the proposed equation.

Detection of vulnerable plaque in a murine model of atherosclerosis with optical coherence tomography

The aim of this study was to evaluate the feasibility of optical coherence tomography (OCT) to identify the components of vulnerable plaques in a well‐established murine model of human atherosclerosis.

Volume Catheter Parallel Conductance Varies Between End-Systole and End-Diastole

In order for the conductance catheter system to accurately measure instantaneous cardiac blood volume, it is necessary to determine and remove the contribution from parallel myocardial tissue. In previous studies, the myocardium has been treated as either purely resistive or purely capacitive when developing methods to estimate the myocardial contribution. We propose that both the capacitive and the resistive properties of the myocardium are substantial, and neither should be ignored. Hence, the measured result should be labeled admittance rather than conductance. We have measured the admittance (magnitude and phase angle) of the left ventricle in the mouse, and have shown that it is measurable and increases with frequency. Further, this more accurate technique suggests that the myocardial contribution to measured admittance varies between end-systole and end-diastole, contrary to previous literature. We have tested these hypotheses both with numerical finite-element models for a mouse left ventricle constructed from magnetic resonance imaging images, and with in vivo admittance measurements in the murine left ventricle. Finally, we propose a new method to determine the instantaneous myocardial contribution to the measured left ventricular admittance that does not require saline injection or other intervention to calibrate.

Drug loading of nanoporous TiO2 films

The loading of therapeutic amounts of drug on a nanoporous TiO(2) surface is described. This novel drug-loading scheme on a biocompatible surface, when employed on medical implants, will benefit patients who require the deployment of drug-eluting implants. Anticoagulants, analgesics and antibiotics can be considered on the associated implants for drug delivery during the time of maximal pain or risk for patients undergoing orthopedic procedures. Therefore, this scheme will maximize the chances of patient recovery.

Enhanced left ventricular systolic function early in type 2 diabetic mice: clinical implications

It is unclear whether the increase in availability of substrates for energy production in diabetes can lead to enhanced systolic function early in the disease, before the onset of structural changes to the myocardium. To examine this issue, BKS. Cg-m +/+ Lepr db (db/db) mice with type 2 diabetes and wild type controls had left ventricular pressure-volume relationships determined in situ. We demonstrated that the db/db mice, when compared to their wild type controls, generated greater left ventricular pressure and an enhancement of left ventricular systolic function based on enhanced power/EDV, positive dP/dt, preload recruitable stroke work, dP/dt — EDV relationship, and curvilinear end-systolic elastance. This enhancement in systolic function occurred despite the db/db mice having greater body weight, but similar preload (end-diastolic volume) and afterload (effective arterial elastance). We postulate that the previously described enhancement in renal glomerular filtration rate seen early in type 2 diabetes may be in part due to enhanced left ventricular systolic function early in this disease.