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The invention relates to the discovery of novel soluble neutral active Hyaluronidase Glycoproteins (sHASEGPs), methods of manufacture, and their use to facilitate administration of other molecules or to alleviate glycosaminoglycan associated pathologies. Minimally active polypeptide domains of the soluble, neutral active sHASEGP domains are described that include asparagine-linked sugar moieties required for a functional neutral active hyaluronidase domain. Included are modified amino-terminal leader peptides that enhance secretion of sHASEGP. The invention further comprises sialated and pegylated forms of a recombinant sHASEGP to enhance stability and serum pharmacokinetics over naturally occurring slaughterhouse enzymes. Further described are suitable formulations of a substantially purified recombinant sHASEGP glycoprotein derived from a eukaryotic cell that generate the proper glycosylation required for its optimal activity.

The invention relates to the discovery of novel soluble neutral active Hyaluronidase Glycoproteins (sHASEGPs), methods of manufacture, and their use to facilitate administration of other molecules or to alleviate glycosaminoglycan associated pathologies. Minimally active polypeptide domains of the soluble, neutral active sHASEGP domains are described that include asparagine-linked sugar moieties required for a functional neutral active hyaluronidase domain. Included are modified amino-terminal leader peptides that enhance secretion of sHASEGP. The invention further comprises sialated and pegylated forms of a recombinant sHASEGP to enhance stability and serum pharmacokinetics over naturally occurring slaughterhouse enzymes. Further described are suitable formulations of a substantially purified recombinant sHASEGP glycoprotein derived from a eukaryotic cell that generate the proper glycosylation required for its optimal activity.

A method and apparatus for analyzing and treating internal tissues and, in particular, tissues affected by myocardial infarct. The apparatus includes a catheterized device integrating an optical probe and treatment delivery system. The probe component includes fiber optic lines that can be used in conjunction with infrared spectroscopy to analyze various characteristics of tissues, including chemical, blood, and oxygen content, in order to locate those tissues associated with myocardial infarct, to determine the best location for applying treatment, and to monitor treatment and its effects. Physically integrated with the probe component is a treatment component for delivering treatments including stem cell and gene therapy, known for having beneficial effects on tissues associated with myocardial infarct. A control system coordinates operation of the catheter, including performing chemometric analysis with the use of model data, and for providing control and visual feedback to an operator.

Disclosed are devices and methods for detecting, preventing, and / or treating neurological disorders. These devices and methods utilize electrical stimulation, and comprise a unique concentric ring electrode component. The disclosed methods involve the positioning of multiple electrodes on the scalp of a mammal; monitoring the mammal's brain electrical patterns to identify the onset of a neurological event; identifying the location of the brain electrical patterns indicative of neurological event; and applying transcutaneous or transcranial electrical stimulation to the location of the neurological event to beneficially modify brain electrical patterns. The disclosed methods may be useful in the detection, prevention, and / or treatment of a variety of indications, such as epilepsy, Parkinson's Disease, Huntington's disease, Alzheimer's disease, depression, bipolar disorder, phobia, schizophrenia, multiple personality disorder, migraine or headache, concussion, attention deficit hyperactivity disorder, eating disorder, substance abuse, and anxiety. The disclosed methods may also be used in combination with other peripheral stimulation techniques.

Methods and apparatus are provided for selective denervation of conduction pathways in the heart for the treatment of dysrhythmias, including one or more ablation or electroporation catheters having electrodes for stimulating, targeting, and ablating fat pad tissue and other cardiac tissue to selectively denervate heart tissue.

The invention is a template to aid in the regeneration of articular cartilage. The template is formed by combining a porous collagen sponge ("collagen matrix") with a dense collagen membrane. The dense collagen membrane is placed on the surface of the cartilage defect to prevent cell migration from the subchondral plate and vasculature. The collagen membrane will allow movement and exchange of fluids, nutrients, cytokines and other factors necessary for cartilage regeneration. The collagen matrix has been developed to allow attachment and growth of cells, specifically chondrocytes which are normally found in articular cartilage. The collagen matrix can be combined with chondrocytes in vitro, and therefore serve to transport cultured cells to the defect site and to retain the cells in position following implantation. Procedures are described to effectively use the two-staged template, and to fix the template to the repair site.

The present invention provides improved methods and apparatus for skin treatment and tissue remodeling. The apparatus includes an array of needles that penetrate the skin and serve as electrodes to deliver radio frequency current or other electrical or optical energy into the tissue being treated, causing thermal damage in controlled patterns. The damaged regions promote beneficial results such as uniform skin tightening by stimulation of wound healing and collagen growth.

The present invention relates to polymeric nanoshells. In certain embodiments, the polymeric nanoshells comprise one or more polymeric shells around a hollow core. In other embodiments, the present invention provides nanoshells useful for the delivery of agents such as, for example, various diagnostic and therapeutic agents.

A system and method for performing fractional resurfacing of a target area of skin using electromagnetic radiation are provided. An electromagnetic radiation is generated by an electromagnetic radiation source. The electromagnetic radiation is caused to be applied to a particular portion of a target area of skin. The electromagnetic radiation can be impeded from affecting another portion of the target area of the skin by a mask. Alternatively, the electromagnetic radiation may be applied to portions of the target area of the skin, other than the particular portion.

A method of relieving analgesia and reducing inflammation using a cannabinoid delivery topical liniment composition containing from about 97.5% to about 99.5% by weight a 70% monohydric alcohol solution, and from about 0.5% to about 2.5% by weight of a synergistic cannabinoid mixture extracted from the female plant Cannabis sativa L, including in combination: 9-Tetrahydrocannabinol (delta-9-THC), 9-THC Propyl Analogue (THC-V), Cannabidiol (CBD), Cannabidiol Propyl Analogue (CBD-V), Cannabinol (CBN), Cannabichromene (CBC), Cannabichromene Propyl Analogue (CBC-V), Cannabigerol (CBG), terpenoids, and flavonoids. The liniment is applied topically, preferably by spraying, and the constituents of the mixture are absorbed through the skin and interact with cannabinoid receptors in the body and tissues of a human patient to produce therapeutic analgesic and anti-inflammatory effects without undesirable psychotropic side effects.

Circulatory assistance is provided in a non-invasive procedure safely and effectively using a microprocessor of an external counter pulsation device programmed to control the actuation of any or all of a plurality of valves, each of which is mounted on and in fluid communication with one of a plurality of individual inflatable bladders disposed in pockets within cuffs encasing the calves, thighs, buttocks, abdomen and / or chest of a person and an optional valve in fluid communication with the person's airway, in any desired sequence or order, toward the heart or toward the feet, either during diastole or systole, at desired inception times during the cardiac cycle, for selected durations and at chosen pressures, for treating a variety of cardiac, non-cardiac and circulatory conditions.

A surgical instrument for ophthalmic surgery, allowing the user to form a uniform circular incision of the anterior lens capsule of an eyeball, as part of an anterior capsulotomy. The capsulectomy device of the preferred embodiment of the present invention has first and second ends, with a rotor emanating from one end, the rotor having a cutting blade or bin situated at the distal end of the rotor, the rotor rotating in pivotal fashion up to 360 degrees, while simultaneously reciprocating the cutting blade at a consistent stroke so as to provide optimal incision edge and depth of the anterior lens capsule of the eyeball. The device is hand held and relatively compact, having provided therein a motor and gear reduction / transmission system for driving the rotor and providing the reciprocating action to the cutting blade or pin. The device further includes a power supply, which is illustrated as a separate component fed to the device via wire, as well as controls for initiating power, as well as varying the speed of the motor. Unlike the prior art systems, which generally have relied upon the skill of the surgeon to perform the radial incision by hand, the present system provides a relatively easy and uniform system for performing the radial incision which is believed to be safer, more uniform, and less time consuming than prior techniques.

Disclosed are therapeutic methods for the treatment of disease material involving administration of a thermotherapeutic magnetic composition, which contains single-domain magnetic particles attached to a target-specific ligand, to a patient and application of an alternating magnetic field to inductively heat the thermotherapeutic magnetic composition. Also disclosed are methods of administering the thermotherapeutic magnetic material composition. The thermotherapeutic methods may be used where the predetermined target is associated with diseases, such as cancer, diseases of the immune system, and pathogen-borne diseases, and undesirable targets, such as toxins, reactions associated with organ transplants, hormone-related diseases, and non-cancerous diseased cells or tissue.

The protective helmet includes a rigid outer shell where the shell includes an undulating cross-sectional profile. A layer of impact-energy-absorbing material is positioned adjacent to the shell. The undulating profile of the shell can be any type of load spreading undulating profile, such as that of a sinusoidal or triangular wave configuration. The undulating load-spreading profile can be on the inner surface of the shell, on the outer surface of the shell or the entire cross-section of the shell may be undulating. The unique undulating profile makes the shell more rigid and spreads the impact load across the surface of the shell to thereby spread the deformation of the padding layer to prevent the shell from bottoming out of the impact-energy-absorbing material during an impact. As a result, a safer and more effective protective helmet is provided.

Disclosed are thermotherapeutic compositions for treating disease material, and methods of targeted therapy utilizing such compositions. These compositions comprise a) stable single domain magnetic particles; b) magnetic nanoparticles comprising aggregates of superparamagnetic grains; or c) magnetic nanoparticles comprising aggregates of stable single magnetic domain crystals and superparamagnetic grains. These compositions may also comprise a radio isotope, potential radioactive isotope, chemotherapeutic agent. These methods comprise the administration to a patient's body, body part, body fluid, or tissue of bioprobes (energy susceptive materials attached to a target-specific ligand), and the application of energy to the bioprobes so as to destroy, rupture, or inactivate the target in the patient. Energy forms, such as AMF, are utilized to provide the energy. The disclosed methods may be useful in the treatment of a variety of indications, including cancers, diseases of the immune system, central nervous system and vascular system, and pathogen-borne diseases.

A contraceptive device for placement in a fallopian tube includes expanding distal and proximal anchor members and an expandable elongate member connecting the distal anchor member to the proximal anchor member. An expandable material is disposed on at least a portion of the contraceptive device, whereupon delivery of the contraceptive device, the expandable material expands to completely occlude the fallopian tube. The expandable material may contain a drug, therapeutic agent, or hormone which is released over time to occlude or otherwise prevent the passage of spermazoa through the fallopian tube, or prevent ovulation. The contraceptive device may be delivered non-operatively and provide complete sterilization within a period of days. The device and delivery method obviates the need for follow-up visits to confirm closure of the fallopian tubes.

A care system and associated methods are provided for alleviating patient pain, anxiety and discomfort associated with medical or surgical procedures, the system comprising: at least one patient health monitor device coupled to a patient and generating a signal reflecting at least one physiological condition of the patient; a drug delivery controller supplying one or more drugs to the patient; a memory device storing a safety data set reflecting parameters of the at least one patient physiological condition; and an electronic controller interconnected between the patient health monitor, the drug delivery controller and the safety data set; wherein said electronic controller manages the application of the drugs in accord with the safety data set. In another aspect of the invention, the care system facilitates a procedural physician's safely and efficaciously providing conscious sedation to a patient by additionally providing a consciousness monitoring-system which monitors the consciousness of the patient and generates a value representing the level of patient consciousness. Methods for alleviating patient pain and anxiety in accordance with the invention comprise connecting a drug delivery device to a patient, such device having a drug delivery controller supplying one or more drugs and being coupled to an electronic controller; attaching at least one patient health monitor device to the patient; accessing a memory device which stores a safety data set reflecting parameters of at least one patient physiological condition; and delivering the drugs to the patient in accord with the safety data set. In further aspects of the invention, the consciousness monitoring system is an automated consciousness monitoring system which includes patient query and response devices. Additional embodiments of the system and methods are directed to alleviating patient pain or discomfort while enabling safe patient controlled drug delivery in correlation with the monitoring of patient health conditions.

Needle-bearing medical devices are provided for fluid infusion, fluid transfusion, and inserting a guide wire. After use the needle is shielded to render the contaminated needle safe to prevent inadvertent needle sticks. The device includes a housing and a needle having a sharpened tip. A biasing element biases the needle toward a position in which the sharpened tip is shielded.

The invention provides polymer compositions for cell and drug delivery.

A method for effecting an oral treatment of teeth and / or gums using an intra-oral device that has a mouthpiece in which is embedded a flexible circuit board and arrays of spaced apart lamps. The mouthpiece has a curvature. The lamps may be light emitting diodes that generate electromagnetic radiation, preferably in the white and blue light spectrum and the infrared and ultraviolet light spectrum. The arrays are positioned to expose the facial and lingual sides of the teeth and / or gums for effecting the treatment when the mouthpiece is positioned to fit upper and lower rows of teeth within accommodating recesses. The flexible circuit board is flexed to exhibit a curvature that follows a curvature of the mouthpiece. Treatments include whitening teeth, desensitizing teeth, and treating gums to prevent periodontal disease.

Needle-bearing medical devices are provided for fluid infusion, fluid transfusion, and inserting a guide wire. After use the needle is shielded to render the contaminated needle safe to prevent inadvertent needle sticks. The device includes a housing and a needle having a sharpened tip. A biasing element biases the needle toward a position in which the sharpened tip is shielded.

An emergency lighting device for providing a directional indication on a recipient surface with first and second guidance indication light sources retained relative to a housing to emit beams of light, each with a directional indication, onto a recipient surface. The light sources can be individually operable and can have directional indications, such as arrows, pointing in first and second different directions. An illumination light source without a guidance indication can illuminate an adjacent area. Guidance indication light sources, which can be lasers, can emit beams in different colors to provide threat level indications. Plural emergency lighting devices can cooperate to guide a building occupant by providing directional indications on recipient surfaces.

Systems, methods, and media for rating websites for safe advertising are provided. In accordance with some embodiments of the disclosed subject matter, the method comprises: extracting one or more features from a piece of web content; applying a plurality of statistical models to the extracted features to generate a plurality of ordinomial estimates, wherein each ordinomial estimate represents a probability that the web content is a member of one of a plurality of severity groups; determining a posterior ordinomial estimate for the web content by combining the plurality of ordinomial estimates; generating a risk rating that encodes severity and confidence based on the determined posterior ordinomial estimate, wherein the risk rating identifies whether the web content is likely to contain objectionable content of a given category; and providing the risk rating for determining whether an advertisement should be associated with the web content.

A method and device selectively and reversibly disrupts the blood-brain barrier (BBB) in a selected volume of the brain without the need for exogenous agents. The method and device employ low intensity directed ultrasound (LODUS) that is safe, reduces the danger of cavitation and thermal tissue damage, and is able to expose small or large regions of the brain to achieve a desired therapeutic or prophylactic effect.

The present invention is directed to compositions and methods for pain management, and for treating inflammation or an inflammation-associated disorder in a subject comprising administering to the subject a therapeutically effective amount of a COX-2 inhibitor and a therapeutically effective amount of a prostacyclin analog, such as treprostinil, a pharmaceutically acceptable salt thereof, or a treprostinil derivative described herein.

A care system and associated methods are provided for alleviating patient pain, anxiety and discomfort associated with medical or surgical procedures. The system comprises: at least one patient health monitor device coupled to a patient and generating a signal reflecting at least one physiological condition of the patient; a drug delivery controller supplying one or more drugs to the patient; a memory device storing a safety data set reflecting parameters of at least one patient physiological condition; and an electronic controller interconnected between the patient health monitor, the drug delivery controller and the safety data set. The electronic controller is capable of effecting a change in the drug supply delivered to the patient and the generation of current signals by the patient health monitor device depending on a comparison between at least one patient physiological condition at its corresponding value reflected in the safety data set.

The present invention provides pyrazine derivatives of formula Iand pharmaceutically acceptable salts thereof, wherein the designation of R1, R2, R3 and R4 is provided herein. The invention also provides syntheses for preparation of such compounds. The invention further provides methods of use of these compounds and pharmaceutical compositions containing them for treatment and / or prevention of diseases and for manufacture of medicaments. These compounds and pharmaceutical compositions have antioxidative and thrombolytic effects, and thus can be used for the treatment and / or prevention of cerebral stroke caused by ischemia, and used for manufacture of medicaments for the treatment and / or prevention of nervous system diseases caused by excessive amount of radicals and / or thrombosis, infectious diseases, metabolic system diseases, cardiovascular and cerebrovascular diseases, and age-related degenerative diseases.

A natural composition formulated to modulate multiple pathophysiological processes in order to facilitate homeostatic glucose metabolism in a patient, and more particularly to increase insulin sensitivity in the same. The natural composition is a safe and effective formulation for the etiological prevention and treatment of diseases, complications, conditions, or disorders associated with chronic or long-term destabilization of glucose metabolism.

A care system and associated methods are provided for alleviating patient pain, anxiety and discomfort associated with medical or surgical procedures. The care system facilitates a procedural clinician's safely and efficaciously providing sedation and analgesia and in some measure, amnesia to a patient by providing a responsiveness monitoring system which monitors the responsiveness of the patient and generates a value representing the level of patient responsiveness. In further aspects of the invention, the responsiveness monitoring system is an automated system which includes patient query and response devices. Additional embodiments of the system and methods are directed to alleviating patient pain or discomfort while enabling safe drug delivery (automated, clinician-controlled or patient-controlled) in correlation with the monitoring of patient health conditions.