Abstract: Compositions and methods for transport or release of therapeutic and diagnostic agents or metabolites or other analytes from cells, compartments within cells, or through cell layers or barriers are described. The compositions include a membrane barrier transport enhancing agent and are usually administered in combination with an enhancer and/or exposure to stimuli to effect disruption or altered permeability, transport or release. In a preferred embodiment, the compositions include compounds which disrupt endosomal membranes in response to the low pH in the endosomes but which are relatively inactive toward cell membranes, coupled directly or indirectly to a therapeutic or diagnostic agent. Other disruptive agents can also be used, responsive to stimuli and/or enhancers other than pH, such as light, electrical stimuli, electromagnetic stimuli, ultrasound, temperature, or combinations thereof.

Abstract: Methods and apparatus for enabling substantially bloodless surgery and for stemming hemorrhaging. High intensity focused ultrasound ("HIFU") is used to form cauterized tissue regions prior to surgical incision, for example, forming a cauterized tissue shell around a tumor to be removed. The procedure is referred to as "presurgical volume cauterization." In one embodiment, the method is particularly effective for use in surgical lesion removal or resection of tissue having a highly vascularized constitution, such as the liver or spleen, and thus a propensity for hemorrhaging. In further embodiments, methods and apparatus for hemostasis using HIFU is useful in both surgical, presurgical, and medical emergency situations. In an apparatus embodiment, a telescoping, acoustic coupler is provided such that depth of focus of the HIFU energy is controllable. In other embodiments, apparatus characterized by portability are demonstrated, useful for emergency medical situations.

Abstract: Methods and apparatus for the remote coagulation of blood using high-intensity focused ultrasound (HIFU) are provided. A remote hemostasis method comprises identifying a site of internal bleeding and focusing therapeutic ultrasound energy on the site, the energy being focused through an intervening tissue. An apparatus for producing remote hemostasis comprises a focused therapeutic ultrasound radiating surface and a sensor for identifying a site of internal bleeding, with a registration means coupled to the radiating surface and the sensor to bring a focal target and the bleeding site into alignment. The sensor generally comprises a Doppler imaging display. Hemostasis enhancing agents may be introduced to the site for actuation by the ultrasound energy.

Abstract: Methods and apparatus for the remote coagulation of blood using high-intensity focused ultrasound (HIFU) are provided. A remote hemostasis method comprises identifying a site of internal bleeding and focusing therapeutic ultrasound energy on the site, the energy being focused through an intervening tissue. An apparatus for producing remote hemostasis comprises a focused therapeutic ultrasound radiating surface and a sensor for identifying a site of internal bleeding, with a registration means coupled to the radiating surface and the sensor top bring a focal target and the bleeding site into alignment. The sensor generally comprises a Doppler imaging display. Hemostasis enhancing agents may be introduced to the site for actuation by the ultrasound energy.