Abstract: The present invention may be embodied in a technique for elimination of vulnerable plaque in a vessel. Vulnerable plaque is detected in the vessel based on a temperature increase of the vessel's wall and treated using cryoablation.

Abstract: A chimeric protein sensor including an optically active polypeptide linked to a responsive polypeptide, or responsive fragment thereof, which undergoes a change in response to a cell signaling event, wherein an optical property of the sensor is altered in response to the change in the responsive polypeptide, or responsive fragment thereof is provided, as well as nucleic acid sequences encoding the chimeric protein sensor. The chimeric protein sensor includes an optically active polypeptide or fragment thereof, such as green fluorescent protein (GFP), for measuring cellular events in vivo.

Abstract: The present invention describes an in vivo method, using pulsed electric field to deliver therapeutic agents into cells of the skin and muscle for local and systemic treatments. In particular, therapeutic agents include naked or formulated nucleic acid, polypeptides and chemotherapeutic agents.

Abstract: Methods are provided for in vivo detection of diseased tissue in a subject, such as tumor tissue located in a body opening, by administering to the subject a biologically compatible fluorescing targeting construct that binds to or is specifically taken up by the diseased tissue. The observer directly views fluorescence emanating from the fluorescing targeting construct bound to or taken up by the diseased tissue upon irradiation of the targeting construct with excitation light having at least one wavelength in the range from 401 nm to about 495 nm, but preferably lacking light having a wavelength above about 500 nm, so as to determine the location and/or surface area of the diseased tissue in the subject. Since excitation wavelength does not penetrate through tissue, as is the practice in near IR diagnostics, the diseased or abnormal tissue is exposed to the excitation light either surgically or by means of an endoscopic device.

Abstract: Methods for aspiration and filtering of a bodily fluid containing undesired components are provided and for treatment of the bodily fluids in a sterile environment in preparation for reinjection of treated aspirate into a donor subject. The invention methods are particularly designed to facilitate transfection of aspirated cells with angiogenesis promoting molecules without danger to the technician or the donor prior to reinjection of the treated cells, either percutaneously or via a surgical opening via a catheter or injection needle. A pressure actuator attached to the sterile container is used to express treated fluids in precisely controlled volumes. The invention methods include delivery of treated fluids using a hand-held device with audible cues that correspond to an operator-selected injection volume and/or audible cues that correspond to needle penetration depth selected by the operator.

Abstract: A flexible stabilizer arm assembly is provided that can be positioned in a desired three-dimensional attitude and then fixed in place to forceably hold an object against an undulating surface. In one embodiment, the invention assembly comprises a mounting base for attachment of the arm to a stationary fixture, a flexible arm of multiple articulated elongate links rotatably joined to adjacent links, a freely rotatable turret joint at the distal end of the arm that is adapted to attach an appendage in freely rotatable fashion to the distal end of the arm. Once positioned, a tightening mechanism is actuated to fix the attitude of the arm with respect to the mounting base. Optionally, the appendage is a two-tined foot adapted for holding a surgical instrument, such as a suction body, against a beating heart. The flexible arm, which ranges up to 12 inches in length, can withstand an undulating force exerted against the distal end of up to 20 pounds while remaining in the fixed position.

Abstract: The present invention provides in vivo methods for detection of vulnerable plaque in a subject in need thereof. In the invention method the subject is administered a diagnostic amount of a biologically compatible detectable lipid-avid agent, the detectable lipid-avid agent is allowed to penetrate arterial walls and attach to any lipid accumulations of oxidized LDL-cholesterol in arterial walls in the wall of an artery; unbound detectable lipid-avid agent is allowed to clear from the body by natural processes, and the presence of the detectable lipid-avid agent attached to the lipid accumulation in the wall of the artery is detected. Detection of bound lipid-avid agent indicates the presence of a vulnerable plaque and predicts a heightened risk of lethal heart attack or thrombus. The detectable lipid-avid agent is selected for its ability to penetrate arterial walls and bind with oxidized LDL-cholesterol in the lipid accumulation in a vulnerable plaque.

Abstract: The present invention may be embodied in a device for detection of vulnerable plaque in a vessel based on a temperature increase of the vessel's wall. The device may be a guide wire having an extendable assembly having resilient delivery wires for placing the temperature sensor in contact with the vessel's inner wall.

Abstract: A method for in vivo electrotherapy, or electroporation-mediated therapy, using a needle array apparatus is provided. Treatment of tumors with a combination of electroporation using the apparatus of the invention, and a chemotherapeutic agent, caused regression of tumors in vivo.

Abstract: A method for in vivo electrotherapy, or electroporation-mediated therapy, using a needle array apparatus is provided. Treatment of tumors with a combination of electroporation using the apparatus of the invention, and a chemotherapeutic agent, caused regression of tumors in vivo.

Abstract: Provided are reagents and methods useful for the synthesis of guanidinylated compounds. Also provided are methods for assaying molecules, including guanidinylated molecules that modulate viral infection and replication.

Abstract: Methods are provided for introducing a biologically active agent into cells of a subject by injecting the agent with a needle-free injector and applying a pulsed electric field to the region of tissue to cause electrotransport of the agent into cells of the tissue. Preferably the agent is either ionized to some degree or contained in an ionized medium for electrotransport. The needle-free injector can serve as an electrode by which the pulsed electric field is applied to the region of tissue. The active agents delivered into cells by this method include small molecules, polynucleotides, polypeptides, and the like. Polynucleotides introduced into cells using this method can be used to accomplish gene therapy or to modulate expression of an endogenous gene.

Abstract: A device for in vivo electroporation therapy comprising an electrode applicator with at least two pairs of electrodes arranged relative to one another to form an array and a power supply. The device is used to generate an electric field in a biological sample and effect introduction of selected molecules into cells of the sample.

Abstract: The present invention provides processes and apparatus for selectively dissolving and removing unwanted solid and semi-solid materials and the like, within a highly localized region utilizing ultra-high energy acoustical waves having a frequency in the range above 50 MHz, for example from about 50 MHz to about 100 GHz. The invention apparatus includes a piezoelectric transducer that is modified to increase the amplitude of acoustical waves of a given frequency without increase in power to the system. The invention and apparatus have important applications in surgical procedures for the treatment of atherosclerotic plaque, prostate disorders, cancers, orthopedic and cosmetic surgery, various types of orthopedic surgery, including atheroscopic surgery, and the like. The present invention is also useful in a wide variety of non-surgical applications, including industrial processes, wherein materials are desired to be selectively removed in a very localized region.

Abstract: The invention provides inexpensive and disposable strapping devices for fixedly binding a supine subject to a rigid board, such as a body board. The invention strapping devices are adaptable to the girth and length of a subject in the range from about 40 pounds to 350 pounds, having straps of adjustable length and adjustable position along the length of the subject and are suitable for use with a subject whose head and/or neck is immobilized in a head block to prevent a potential shearing point at the neck of the subject. In another embodiment, the invention provides heavy duty reusable strapping devices for securely strapping a patient into a litter, such as a Stokes basket, for transport. The heavy duty litter strapping devices are adjustable to the size of the subject and are quick and easy to apply, but are of sufficient strength to be utilized in emergency rescue situations.

Abstract: The present invention provides a flexible suction body and method of its use for temporarily immobilizing a local area of tissue during surgery or a diagnostic procedure. The invention device and method are particularly well suited for immobilizing a local area of heart tissue to thereby permit surgery, for example, minimally invasive or micro-surgery, on a coronary vessel without significant deterioration of the pumping function of the beating heart. The invention suction device, which is coupled to a vacuum source, has a ring- or horseshoe-shaped suction channel with a flexible, spreadable outer rim that flattens and spreads outwardly against the surface of the treatment site as air is withdrawn from the suction channel. This design distributes the pressure of the suction body against the treatment site while maximizing the suction field to minimize bruising and suction hemorrhage at the treatment site caused by the suction body.

Abstract: Methods are provided for in vivo detection of tissue associated with a disease state in a subject, such as tissue located in a body opening. In the invention method, the subject is administered a biologically compatible fluorescing targeting construct, the construct is allowed to bind to any target tissue present in the subject, a body part of the subject suspected of containing the target tissue is irradiated with UV light while extraneous light to the body part is substantially eliminated, and fluorescence emanating from the fluorescing targeting construct bound to the target tissue is detected and visualized by the observer with or without the aid of an endoscope, so as to determine the location and size of the target tissue. The invention methods offer the advantage that diseased or abnormal tissue can be detected at interior body sites with or without the aid of an endoscopic device.

Abstract: Methods are provided for in vivo detection of tumor tissue associated with a disease state in a subject, such as tumor tissue located in body opening. In the invention method, the subject is administered a biologically compatible fluorescing targeting construct, the construct is allowed to bind to and/or be taken up by tumor tissue present in the subject, a body part of the subject suspected of containing the tumor tissue is irradiated with UV light while extraneous light to the body part is substantially eliminated, and fluorescence emanating from the fluorescing targeting construct bound to and/or taken up by the tumor tissue is directly viewed by the observer with or without the aid of an endoscope, so as to determine the location and size of the tumor tissue.

Abstract: Nitric oxide scavengers, such as dithiocarbamate-containing compounds, are used to reduce side effects caused by therapeutic administration of nitric oxide sources by administering the nitric oxide scavenger(s) to the subject after the therapeutic effect of the nitric oxide source has been achieved. For example, the nitric oxide source can be coadministered with the nitric oxide scavenger, with the latter formulated in a time release vehicle selected to delay release of the scavenger for a period of time sufficient to ensure that the therapeutic goal of the nitric oxide source has been achieved before release of the scavenger. Formulations and kits, including a bubble pack with pairwise arrangement of unit doses of a desired nitric oxide source and nitric oxide scavenger, are also provided.

Abstract: The present invention provides stabilizing devices and methods of use for temporarily remotely immobilizing a local area of tissue, such as a local area of tissue on a beating heart, or other internal organ, to thereby permit minimally-invasive or robotic surgery thereon. The invention stabilizing device, which is coupled to a vacuum source, features an elastomeric suction body mounted on the steerable tip of a rod-like instrument, such as a steerable catheter. The flexible or steerable tip and elongate suction channel are sized for introduction into an interior body cavity via a small surgical opening. A steering mechanism mounted at the proximal end of the device is used to coil the elongate tip and suction channel into a ring- or horseshoe-shape within the body cavity.