Abstract: Systems and methods are disclosed for the treatment of a target tissue by directionally delivering energy and/or bioactive materials to achieve a therapeutic effect. A balloon catheter system having a balloon portion and a plurality of electrodes may be energized to selectively deliver energy, bioactive materials, or a combination thereof to target tissue including tissues disposed about a lumen. The tissue may be targeted by applying energy, making tissue impedance analysis, and further selectively energizing electrodes through the use of an energy source with a controller.

Abstract: Methods of iontophoretically delivering therapeutic agents to diseased tissue, such as for tumor therapy, are disclosed. In one embodiment, the distal end of an endoscopic device is transorally introducing into the gastro-intestinal tract. A delivery element is advanced from the endoscopic device through a wall of the gastro-intestinal tract and into an adjacent pancreas. A therapeutic agent is delivered from the delivery element into the pancreas, an electric field is generated to drive the emitted therapeutic agent into surrounding tissue of the pancreas, causing the emitted agent to penetrate the surrounding tissue.

Abstract: A drug delivery apparatus guided by micro electrical field network for target cells of liver comprises a low-voltage micro- electrical field generator and a drug delivery catheter which gets into a liver through an endoscope or indwelling catheter along blood vessels, wherein at least two drug infusion holes and a first array of electrodes are provided at the front end of the drug delivery catheter; a second array of electrodes is set on the exterior of the liver; the first array of electrodes and the second array of electrodes are connected with the pulse output terminal of the low-voltage micro-electrical field generator; the drug delivery catheter is connected through with a drug transportation device.

Abstract: A device, a system, or a method is described for treating a disease or a condition of one or more joints of articulating bone in a mammalian subject. The device provides one or more medicaments to one or more joints of the mammalian subject. A device is described that includes one or more sheaths configured to contact one or more body contours in proximity to one or more joints of articulating bone of a mammalian subject; one or more sensors configured to detect one or more physiological conditions of the one or more joints; and one or more applicators supported by the one or more sheaths and configured to respond to the one or more sensors by injecting one or more medicaments to the one or more joint tissues of the mammalian subject.

Abstract: An apparatus and method for performing non-invasive treatment of the human face and body by electroporation in lieu of cosmetic surgery is provided. The apparatus comprises a high voltage pulse generator and an applicator having two or more electrodes in close mechanical and electrical contact with the patient's skin for applying the pulses to the patient's skin. The applicator may consist of two pieces with one electrode having a sharp tip and another having a flat surface. High voltage pulses delivered to the electrodes create at the tip of the sharp electrode an electric field high enough to cause death of relatively large subcutaneous fat cells by electroporation. Moving the electrode tip along the skin creates a line of necrotic subcutaneous fat cells, which later are metabolized by the body. Multiple applications of the electrode along predetermined lines on the face or neck create shrinkage of the skin and the subcutaneous fat volume underlying the treated area.

Abstract: Methods and apparatus are provided for inducing, monitoring and controlling renal neuromodulation using a pulsed electric field to effectuate electroporation or electrofusion. In some embodiments, tissue impedance, conductance or conductivity may be monitored to determine the effects of pulsed electric field therapy, e.g., to determine an extent of electroporation and its degree of irreversibility. Pulsed electric field electroporation of tissue causes a decrease in tissue impedance and an increase in tissue conductivity. If induced electroporation is reversible, upon cessation of the pulsed electric field, tissue impedance and conductivity should approximate baseline levels; however, if electroporation is irreversible, impedance and conductivity changes should persist. Thus, monitoring of impedance or conductivity may be utilized to determine the onset of electroporation and to determine the type or extent of electroporation.

Abstract: A method is disclosed for delivering molecules such as pharmaceutical drugs and nucleic acids into skeletal muscle in vivo. The molecule is first injected into the muscle at one or multiple sites. Immediately or shortly after injection, electrodes are placed flanking the injection site and a specific amount of electrical current is passed through the muscle. The electrical current makes the muscle permeable, thus allowing the molecule to enter the cell. In the case where nucleic acid is injected, the efficiency of transfer permits expression of protein encoded by the nucleic acid in an amount that exhibits systemic biological activity and which generates a robust immune response.

Abstract: According to one embodiment, a transdermal drug administration apparatus includes a first member having a protrusion on a facing surface opposed to a skin and a guide hole in the protrusion and a second member having a needle portion located in the guide hole and movable in a first direction across a surface of the skin.

Abstract: Disclosed herein is a device for skin treatment, which precisely transmits high-frequency energy to a target portion of skin tissue without causing a burn on the outer layer of the skin, thus artificially damaging the portion and inducing a wound curing reaction, therefore leading to the regeneration of skin and the propagation of collagen. The device prevents the surface of skin from suffering an injury during insertion, alleviates pain, and keeps the depth to which the needle is inserted into the skin uniform. The device includes a plurality of needles coated with an insulator except for sharp ends. A needle holding unit holds the needles. A drive unit directly or indirectly transmits a force to the needle holding unit, thus allowing the needles to be inserted into the skin. An electromagnetic wave transmitting unit is electrically connected to the needles and transmits electromagnetic waves to the needles.

Abstract: Intralumenal devices and methods are provided for transmucosal drug delivery. The device may comprise a housing configured for intralumenal deployment into a human or animal subject; a drug-dispensing portion which contains at least one drug; and an electrically-actuatable portion configured to disrupt at least one region of a mucosal barrier adjacent to the housing at a selected time while intralumenally deployed in the human or animal subject. The device may be operable to dispense the drug from the housing to a region of the mucosal barrier disrupted by the electrically-actuatable portion.

Abstract: An irrigation ablation probe comprises a generally rigid probe body and a handle mounted to the proximal end of the probe body. The generally rigid probe body comprises an ablation electrode at its distal end having at least one irrigation opening through which fluid can pass. An infusion tube extends through the probe body for introducing fluid into the ablation electrode. The irrigation ablation probe is useful for treating atrial fibrillation during open heart surgery.

Abstract: Apparatus and methods in which very small volumes of biological fluid-borne material, particularly large molecules such as proteins, may be selectively extracted from or delivered to interstitial fluid (in vivo or in vitro) by means of intra-parenchymal micro-probes inserted in the brain. The primary use of the micro-probe is in neuroscience research, clinical diagnostics or treatment of epilepsy and other neurological conditions; it may also be applied to other organs and biological systems. Eventual human clinical applications may include neurosurgical monitoring, functional tracking of devices or materials introduced in a surgical procedure, or cerebro-spinal fluid sampling.

Abstract: A system for applying a polymer (hydrogel) to the inner surface of a vessel by photopolymerization includes a catheter having a first inflatable member and a guidewire having a second inflatable member. The catheter has an extended tip distal to the first inflatable member that includes multiple perfusion ports. A light emission coil is disposed on the extended tip with individual coil loops interspaced with the perfusion ports. In a method, the guidewire is delivered to a treatment site within a vessel. The catheter is delivered to the treatment site over the guidewire. The inflatable members are inflated to form an enclosed treatment space within the vessel. A photoinitiator is delivered to the enclosed treatment space. Excess photoinitiator is flushed from the treatment space, and a prepolymer is delivered. The prepolymer is cured by light delivered by the light emission coil.

Abstract: The present invention provides an apparatus and a method for generating and applying an electric field according to a user configured arbitrary waveform pulsing train. A control module allows the user to input operation parameters and configure the arbitrary waveform pulsing train for the electroporation process. A micro-controller unit coupled to the control module controls an arbitrary waveform generator unit and a customized power module. During the electroporation process, the arbitrary waveform generator unit produces the arbitrary waveform pulsing train that is amplified by the customized power module. The customized power module is coupled to at least two electrodes, wherein the at least two electrodes will produce an electric field across a target media.

Abstract: The present invention provides apparatus and methods for the delivery of therapeutic agents to target tissues by electromigration. The utilization of electric fields according to the methods of the invention aids in the distribution and targeting of therapeutic agents, in particular, where standard means of agent application in the target tissue is insufficient to achieve prophylactic or therapeutic results. In particular embodiments, the present invention utilizes a convective force in combination with the developed electric fields to further increase the flux of the therapeutic agent or to further improve distribution of the therapeutic agent within the target tissues.

Abstract: The invention provides an endoscopic imaging photodynamic therapy system (EIPS) for focused tissue ablation by illumination of a photosensitizer drug in a target tissue, said system comprising an endoscopic assembly, a real-time imaging component for locating the target tissue and monitoring the ablation intervention, a therapeutic light system and, optionally, a drug delivery module, wherein said imaging component comprises a flexible transducer with an operative channel for insertion of a flexible light guide of the therapeutic light system and, optionally, a flexible drug delivery catheter of the drug delivery module. This EIPS may be used in various medical applications where tissue ablation is required and photodynamic therapy may be applied, in particular, in the treatment of extrauterine pregnancy (EUP).

Abstract: Exemplary method and apparatus can be provided for directing a substance and electromagnetic radiation to a particular location in a biological tissue, for example, to inject and cure a cosmetic filler in situ. The apparatus can include a needle configured to be inserted into the tissue, and a waveguide configured to direct the electromagnetic radiation, such as optical energy, to a location proximal to the needle tip. The substance can be injected into the tissue through the needle and irradiated by the optical energy. In addition, the exemplary method and apparatus can be provided for determining the location of the needle tip in a biological tissue based on characteristics of light directed through the waveguide and emitted proximal to the needle tip. For example, intensity of the emitted light can indicate whether the needle tip is located inside or outside of a blood vessel.

Abstract: This invention comprises an improved electroporation electrode system comprising a single needle and a ring or donut shaped electrode wherein the difference in surface area of the electrodes provide for a substantial reduction of current density near the surface of the treated tissue and a more concentrated current density sufficient for electroporation only in tissues adjacent to the terminal portion of the single needle electrode. Thus, this invention provides for targeting specific tissue for electroporation and also should provide for lessening the sensation of electric current in the treated tissue.

Abstract: The present embodiments provide an elongate medical device comprising a plurality of strands twisted in a generally helical manner to form a tubular shape having a longitudinal axis. A first strand of the plurality of strands is moveable with respect to at least a second strand of the plurality of strands. Actuation of the one or more strands may perform a medical function or actuate an associated distal component. A working lumen of the tubular member may remain unobstructed for delivery of medical components or fluids.

Abstract: Medical electrical lead systems and related methods are described. The medical electrical lead systems may be configured to be at least partially implanted in a body of a subject. Some variations of the medical electrical lead systems may comprise a lead body comprising a proximal end and a distal end and a lumen extending at least partially therebetween, at least one electrode in the proximity of the distal end of the lead body, and a reservoir in fluid communication with the lumen, where the reservoir is located at a position removed from the distal end of the lead body. Certain variations of the medical electrical lead systems may comprise a lead body comprising a proximal end and a distal end and first and second lumens extending at least partially therebetween, and at least one electrode in the proximity of the distal end of the lead body.

Abstract: A method is provided for treating a dermatological wound. A first step of the method includes providing an iontophoretic apparatus. The iontophoretic apparatus includes at least one surface for contacting a surface of the dermatological wound, a current source electrically coupled to the apparatus, a suction mechanism operably coupled to the apparatus, and a source of therapeutic molecules. A second step of the method includes placing the at least one surface of the iontophoretic apparatus into contact with at least a portion of the dermatological wound surface. A third step of the method includes activating the current source so that a plurality of therapeutic molecules is delivered to the dermatological wound. A fourth step of the method includes activating the suction mechanism to remove fluid and/or debris from the dermatological wound. The second, third, and fourth steps of the method are repeated until the dermatological wound is sufficiently healed.

Abstract: A medical tubular body that may be used in an implantable medical lead, a catheter, a sheath and introducer is disclosed herein. The medical tubular body may include a tubular layer formed of an electrically insulating polymer and an electrically conductive polymer strip imbedded in and longitudinally extending through the insulating polymer.

Abstract: A therapeutic agent delivery device and method for eluting a therapeutic agent to a target location are disclosed. The device may comprise a first conductive element, a second conductive element, an electrochemical composition including an electrolyte and a therapeutic agent, and a permeable membrane covering the electrochemical composition. The first conductive element and the second conductive element are adapted to be connected to a voltage source. When the voltage source is connected to the first conductive element and the second conductive element, an electrochemical reaction occurs causing the therapeutic agent to pass through the permeable membrane and thereby to elute to a target location.

Abstract: The invention concerns a device for the extracorporeal irradiation of a patient's (P) bodily fluid containing bilirubin, comprising a first (10) and a second (12) line which can be connected to the patient (P), an impermeable irradiation unit for bodily fluids (14) connected therewith and located between the first (10) and the second (12) lines, and at least one adjustable feed unit for bodily fluids (16) located in the first (10) and/or the second (12) line, wherein by means of at least one feed unit for bodily fluids (16) an adjustable flow of bodily fluid through the lines (10, 12) and the irradiation unit for bodily fluids (14) is achievable, in which the first line (10) is designed to continually circulate the bodily fluid drawn from the patient (P) and route it to the irradiation unit for bodily fluids (14), and the second line (12) is designed to continually circulate the irradiated bodily fluid to the patient (P), and in which the irradiation unit for bodily fluids (14) contains an radiation source fo

Abstract: A liquid injector displays a plotting chart image whose vertical axis represents liquid injection rates and horizontal axis represents liquid injection times. When an injection graph which represents a liquid injection rate at each quantity of the liquid to be injected is entered into the displayed plotting chart image, the liquid injector controls operation of an injection performing means according to the injection graph and a time which has elapsed from the start of injection of the liquid. The rate at which the liquid is injected can thus be changed as desired with time according to the injection graph.

Abstract: The instant invention provides a method for improving efficiency of RNA delivery to cells. The method comprises applying a low strength electric field to the cells and then after a certain time period, administering the ribonucleic acid sequence to the cells. Devices, kits, and RNA molecules suitable for delivery and devices suitable for practicing the disclosed methods are also provided.

Abstract: The instant invention provides a method for improving efficiency of RNA delivery to cells. The method comprises applying a low strength electric field to the cells and then after a certain time period, administering the ribonucleic acid sequence to the cells. Devices, kits, and RNA molecules suitable for delivery and devices suitable for practicing the disclosed methods are also provided.

Abstract: A system, method, and apparatus for iontophoretically delivering medically-active ions beyond the tympanic membrane, into a middle ear portion of a patient, and to an area or structure of the middle or inner ear that is targeted for treatment. The system and apparatus can include a needle configured partially for insertion through a tympanic membrane and having a longitudinal bore, a flexible lumen coupled with the needle, and typically a fluid source coupled with the lumen such that a fluid in the fluid source can be delivered from the fluid source, through the lumen and the needle, and into the middle ear. A positioning tab can be coupled with the needle to assist determining a proper insertion extent of the needle through the membrane.

Abstract: Embodiments of the present invention are directed to systems, apparatuses, devices and methods for improving, modifying and/or stabilizing pharmacokinetic and/or pharmacodynamic profile of a drug infused into the tissue by a catheter and absorbed into the blood or lymphatic system. In some embodiments, infusion sets provide fluid and electrical connection between a catheter assembly/treatment element and at least one of a fluid source and a second source.

Abstract: A prostate gland electrochemical-therapeutic device is provided. The prostate gland electrochemical-therapeutic device includes a probe unit and an electrode unit. The probe unit is adapted for introducing a saline solution into a patient's prostate gland. The electrode unit then conducts an electrochemical reaction on the saline solution introduced in the prostate gland to generate a strong acid solution and/or a strong alkaline solution for curing the prostate gland thereby.

Abstract: A device and method for safely securing a multilumen device to a tissue, organ or solid tumor within the body of a human during a diagnostic or therapeutic procedure is described. The device is capable of securing the tumor by touching or piercing its surface and providing a coolant to the distal tip. Cooling the tip forms a cryogenically induced region that tightly binds the tip to the tumor, temporarily sealing the entry-track of the instrument. The device further provides at least one injecting/aspirating lumen that can dispense or aspirate a fluid within the tumor, and an outer sheath or guide. Such construction allows injecting part or whole volume of the tumor while the cryogenically induced bond prevents back-flow of the injected substances through the entry-track.

Abstract: An intracranial implant emitting light having a wavelength between blue and yellow light

Abstract: Methods and apparatus are provided for intravascularly-induced neuromodulation using a pulsed electric field, e.g., to effectuate irreversible electroporation or electrofusion, necrosis and/or inducement of apoptosis, alteration of gene expression, changes in cytokine upregulation, etc., in target neural fibers. In some embodiments, the intravascular PEF system comprises a catheter having a pair of bipolar electrodes for delivering the PEF, with a first electrode positioned on a first side of an impedance-altering element and a second electrode positioned on an opposing side of the impedance-altering element. A length of the electrodes, as well as a separation distance between the first and second electrodes, may be specified such that, with the impedance-altering element deployed in a manner that locally increases impedance within a patient's vessel, e.g.

Abstract: Devices, systems, and methods are described herein for controlling or modulating the levels of one or more target components in the blood and/or lymph of a vertebrate subject. Devices and systems are provided that include a body defining at least one lumen configured for fluid flow; at least one controllable flow barrier to fluid flow into the at least one lumen; at least one first reservoir disposed within the body and configured to include one or more bifunctional tags, wherein the one or more bifunctional tags are configured to selectively bind to one or more target components in one or more of blood fluid or lymph fluid of a vertebrate subject; at least one treatment region disposed within the at least one lumen; and at least one second reservoir disposed in the at least one treatment region and configured to include one or more reactive components, wherein the one or more reactive components are configured to sequester the one or more bifunctional tags when bound to the one or more target components.

Abstract: A method for creating an autologous radiofrequency capsule for containing filling solutions, whose particularity is that it comprises the combined use of bipolar radiofrequencies and of filling or bio-revitalizing solutions based on hyaluronic acid or similar products.

Abstract: Photodynamic bone stabilization systems are disclosed herein. In an embodiment, a photodynamic bone stabilization system includes a catheter having an elongated shaft with a proximal end adapter, a distal end releasably engaging an expandable portion, and a longitudinal axis therebetween; a light-conducting fiber configured to transmit light energy to the expandable portion; a light-sensitive liquid monomer comprising an initiator, wherein the initiator is activated when the light-conducting fiber transmits the light energy to initiate polymerization of the light-sensitive liquid monomer; and a cooling medium configured to control polymerization temperature, wherein the catheter comprises an inner void sufficiently designed to pass the light-sensitive liquid monomer into the expandable portion, and wherein the catheter comprises an inner lumen sufficiently designed to pass the light-conducting fiber into the expandable portion and configured to circulate the cooling medium.

Abstract: The present invention is directed towards materials and methods of delivering biomolecules to cells that define an organ, and the organ being in situ, and electroporating cells defining the organ by delivering to the cells an amount of energy effective to electroporate the cells. The present invention is also directed towards materials and methods of expressing heterologous polypeptides in organs of a subject and electroporating cells defining the organ by delivering to the cells an amount of energy effective to electroporate the cells.

Abstract: A catheter is comprised of a flexible cylindrical tube defining a proximal portion and a distal portion terminating in a distal tip. The tube has a plurality of openings formed therethrough to form a diffusion area. The catheter includes a conductive end cap enclosing a distal tip. A flexible conductive member is attached to the conductive end cap and extends to the proximal portion where it is attached to the inside diameter of the flexible tube. The member is movable within the tube. Because of the rules governing abstracts, this abstract should not be relied upon in construing the claims.

Abstract: A dermatological skin treatment device is provided. The device comprises a handpiece and a cutting tool, wherein the tool is inserted through the conduit and percutaneously inserted into a tissue disposed within a recessed area of the handpiece. The device and method cut the fibrous structures under the skin that cause cellulite at an angle substantially parallel to the surface of the skin and replace these structures with a non-cellulite forming structure by deploying a highly fibrous mesh through a single needle hole to create a highly fibrous layer directly or through wound healing processes.

Abstract: A device for manipulating a molecule in vivo relative to a target tissue includes at least one elongated member having at least two discrete and separately activatable electrodes separated by an insulating material interposed therebetween. The electrodes are configures to establish at least one of a first electromagnetic field between selected electrodes sufficient to manipulate a molecule relative to a target tissue and a second, typically higher-level, electromagnetic field sufficient to cause transient permeability of a cell membrane within the target tissue. A third electromagnetic field may also be applied to cause further translation of the molecule into an electropermeabilized cell and/or manipulated with respect to the tissue. Thus three-dimensional manipulation of the molecule relative to the target tissue may be effected to optimize a desired positioning thereof, such as entry into a cell.

Abstract: A transparent illuminated infusion cannula is provided for illuminating an area during eye surgery. An optical fiber may be spaced a certain distance away from the cannula such that fluid flow around the distal end of the fiber and into the transparent cannula may occur with a much higher flow rate than what had previously been possible. The fiber cannula airspace may be optimized so that the cross-sectional area of the fluid conduit remains substantially constant in order to achieve a best compromise between high light transmittance and high fluid flow rate.

Abstract: A medical device for placement of regional anesthesia catheters. The device comprises a hollow shaft needle, a plunger attached to the posterior end of the needle, a housing dimensioned so that plunger can slide inside the housing with friction, a regional anesthesia catheter preloaded inside the needle, a protective cover sheath covering the catheter, and a catheter adaptor attached to posterior end of the sheath and the catheter. The medical device allows a practitioner to quickly and effectively place a regional anesthesia catheter inside an organism without the use of an assistant, and with minimal risk of contaminating the catheter before it enters the organism's body. At the end, the needle is withdrawn inside the housing and disposed.

Abstract: A medical device, in particular for electroporation treatment, characterized by having: a thimble-like main body fitted, in use, to a hand of an operator; and a member connected to the main body and fitted with needles by which the operator performs the therapeutic treatment.

Abstract: A method for forestalling or therapy, at least partially, of BPH or prostate cancer comprising identifying a reflux of venous blood to the prostate and impeding the reflux by treating veins effecting or conveying the reflux, and related apparatus and kit.

Abstract: A catheter system for delivering ultrasonic energy to a treatment site within a body lumen comprises a tubular body. The tubular body has a proximal end, a distal end and an energy delivery section positioned between the proximal end and the distal end. The catheter further comprises an inner core configured for insertion into the tubular body. The inner core comprises a first ultrasound radiating member axially separated from a second ultrasound radiating member by an intermediate flexible joint region. The inner core further comprises an electrically conductive portion configured to allow a voltage difference to be applied to at least one of the ultrasound radiating members. The inner core further comprises a high impedance cap positioned proximal to at least one of the ultrasound radiating members.

Abstract: A system and method for use in iontophoretic anesthesia of a tympanic membrane are disclosed. The system generally includes an earplug and an electrode device. The earplug includes at least one sealing member for sealing the earplug in an ear canal. The sealing member includes microholes which vent fluid above a certain pressure threshold. A headset may connect the earplug to a second earplug. The method involves using the system on a human or animal subject.

Abstract: A thrombolysis catheter apparatus is disclosed comprising: (a) an elongated thrombolysis catheter portion comprising a plurality of independently controllable electroactive polymer actuators, which provide a curvature to the thrombolysis catheter based upon received control signals; (b) a control unit coupled to the plurality of actuators and sending the control signals to the plurality of actuators; and (c) an occlusion removal device. Also disclosed is a method of treating an arterial occlusion by advancing the thrombolysis catheter portion through the arterial vasculature of a patient to a position proximate the occlusion, while controlling the shape of the thrombolysis catheter portion using the control unit. The occlusion is then removed using the occlusion removal device.

Abstract: Apparatuses and methods for the safe and efficient electrical stimulation of tissue. The apparatuses of the present invention are preferably hand-held and are capable of providing electrical waveforms that are effective in promoting wound healing, improving circulation, stimulating peripheral nerves, administering pharmaceutical compounds via electrophoresis, and electroporating DNA into tissue. The present invention also generally contemplates the safe and efficient transfection of DNA into mammalian tissue via electroporation. Particularly, apparatuses of the present invention are useful in the delivery of DNA vaccines and in gene therapy. The present invention also preferably provides for the direct measurement of in vivo tissue resistance. Tissue resistance measurements may then be used to adjust stimulation intensity during electroporation or electrostimulation, so as to avoid damaging tissue during operation of the unit.

Abstract: A treatment system for surgery includes: a handpiece driving apparatus for supplying electric energy to a handpiece, the handpiece including a treatment portion insertable into a body cavity; a perfusion apparatus for perfusing liquid in the body cavity, the perfusion apparatus being capable of adjusting pressure in the body cavity; and a control circuit for controlling the pressure in the body cavity to a different level in conjunction with an output state of the handpiece driving apparatus and changing a flow rate of the perfusion liquid.

Abstract: A treatment assembly is positioned along an AV-fistula and couples therapeutic energy to an adjacent area due to a material response to an applied energy field from a remotely located energy source. The treatment assembly may be delivered into the fistula through a hemodialysis needle, or may be secured to the fistula graft itself and implanted therewith in a patient. A cover provides a shield between an anastomosis area and blood flow. Another AV-fistula includes a valved reservoir that receives a fluid agent from a hemodialysis needle while moving the needle into or from the fistula; the agent leaks from the reservoir into the fistula lumen. Another valved fistula is adjustable between an open condition and closed conditions during and between hemodialysis treatments, respectively. Another AV-fistula has a bladder reservoir coupled to a second refillable fluid reservoir and is adapted to locally deliver a therapeutic agent into the fistula lumen.