Development of the Metronomic Biofeedback Pump for leptomeningeal carcinomatosis: technical note.

Patients with leptomeningeal carcinomatosis face a particularly grim prognosis. Current treatment consists of intrathecal delivery of methotrexate (MTX) or cytosine arabinoside (Ara-C) via Ommaya reservoir or lumbar puncture. Yet despite these interventions, the median survival after diagnosis is only 4-7 months. To address inherent shortcomings of current treatments and provide a more effective therapeutic approach, the Pharmaco-Kinesis Corporation has developed a novel type of implantable pump capable of delivering intrathecal chemotherapy (i.e., MTX) in a metronomic fashion with electronic feedback. The Metronomic Biofeedback Pump (MBP) consists of 3 components: 1) a 2-lumen catheter; 2) a microfluidic delivery pump with 2 reservoirs; and 3) a spectrophotometer monitoring MTX concentrations in the CSF. Using an animal model of intraventricular drug delivery, the authors demonstrate that the MBP can reliably deliver volumes of 500 µl/min, consistently measure real-time intrathecal MTX concentrations via CSF aspiration, and provide biofeedback with the possibility of instant control and delivery adjustments. Therefore, this novel approach to chemotherapy minimizes toxic drug levels and ensures continuous exposure at precisely adjusted, individualized therapeutic levels. Altogether, application of the MBP is expected to increase survival of patients with leptomeningeal carcinomatosis, and appropriate Phase I and II trials are pending.

Non-Fluoroscopic Transseptal Catheterization During Electrophysiology Procedures using a Remote Magnetic Navigation System.

Transseptal punctures are commonly performed, and left atrial (LA) access is frequently lost during lengthy, complex electrophysiology (EP) procedures. We describe a new technique for non-fluoroscopic re-crossing the fossa ovalis using a new multielectrode transseptal sheath (TS) and a new remote magnetic catheter navigation system (RMNS) (CGCI System, Magnetecs) that uses 8 rapid external electromagnets for real-time navigation of a magnet-tipped electrode catheter across the initial transseptal puncture site in 5 patients undergoing left-sided ablation procedures. The three-dimensional (3D) position of a 8.5 Fr steerable TS with 5-ring 5-15-15-5-mm spaced distal electrodes (Agilis ES©, St Jude Medical), and site of fossal ovalis crossing were "shadowed landmarks" on a 3D electroanatomic mapping (EAM) system (EnSite/NavXTM, St Jude Medical). The TS-magnetic ablation catheter assembly was pulled-back to the inferior vena cava. EAM landmarks were used with RMNS-guided "manual" and "automated" catheter navigation modalities, until septal crossing was obtained. Transseptal re-crossing was successfully performed in all patients in 6.2±8.1 sec using the "automated" RMNS-guided technique and in 30.4±28.4 sec using the "manual" RMNS-guided technique (p=0.01) without complications. This new RMNS was safely and effectively used to perform non-fluoroscopic transseptal catheterization.

Dynamically shaped magnetic fields: initial animal validation of a new remote electrophysiology catheter guidance and control system.

BACKGROUND: To address some of the shortcomings of existing remote catheter navigation systems (RNS), a new magnetic RNS has been developed that provides real-time navigation of catheters within the beating heart. The initial experience using this novel RNS in animals is described. METHODS AND RESULTS: A real-time, high-speed, closed-loop, magnetic RNS system (Catheter Guidance Control and Imaging) comprises 8 electromagnets that create unique dynamically shaped ("lobed") magnetic fields around the subject's torso. The real-time reshaping of these magnetic fields produces the appropriate 3D motion or change in direction of a magnetized electrophysiology ablation catheter within the beating heart. The RNS is fully integrated with the Ensite-NavX 3D electroanatomic mapping system (St Jude Medical) and allows for both joystick and automated navigation. Conventional and remote navigational mapping of the left atrium were performed using a 4-mm-tip ablation catheter in 10 pigs. A multielectrode transseptal sheath allowed for additional motion compensation. Linear and circumferential radiofrequency lesion sets were performed; in a subset of cases, selective pulmonary vein isolation was also performed. Recording and fluoroscopic equipments were unaffected by the magnetic fields generated by Catheter Guidance Control and Imaging. Automated mode navigation was highly reproducible (96±8.4% of attempts), accurate (1.9±0.4 mm from target site), and rapid (11.6±3.5 seconds to reach targets). At postmortem examination, radiofrequency lesion depth was 78.5±12.1% of atrial wall thickness. CONCLUSIONS: A new magnetic RNS using a dynamically shaped magnetic field concept can reproducibly and effectively reach target radiofrequency ablation points within the pig left atrium. Validation of the system in clinical settings is under way.

Vaccination with E. coli recombinant empty viral particles of infectious bursal disease virus (IBDV) confer protection.

The A genome segment of the highly virulent Infectious bursal disease virus (IBDV) was amplified using long and accurate-RT-PCR (LA-RT-PCR). The entire sequence region encoding VP2, VP4, and VP3 in that order was cloned and sequenced. Following subcloning into the Escherichia coli expression vector pET21a under the T7 promoter, viral proteins were expressed and processed as demonstrated by Western blot analysis. Virus-like particles could be visualized by immuno-electron microscopy in IPTG-induced cells suggesting that viral assembly can take place in E. coli. Induction of anti-IBDV antibodies was detected in chickens immunized with purified recombinant IBDV by intra muscular (i.m.) injection. Furthermore, the vaccinated chickens were protected when challenged with the Gep 5 isolate of IBDV.