Abstract: The object of the present invention is a liquid atomization procedure that uses appropriate geometric parameters and physical properties to ensure that the liquid to be atomized is discharged as a continuous, steady capillary microjet through a suitable orifice. The procedure relies on the microwithdrawal effect undergone by a liquid-gas interface when the gas is withdrawn from a point (orifice) near the liquid surface. The invented procedure is applicable to any mechanism involving homogeneous atomization of liquids (particularly electronic fuel injection).

Abstract: The invention is directed to a stable capillary microjet and a monodisperse aerosol formed when the microjet dissociates. A variety of devices and methods are disclosed which allow for the formation of a stream of a first fluid (e.g. a liquid) characterized by forming a stable capillary microjet over a portion of the stream wherein the microjet portion of the stream is formed by a second fluid (e.g. a gas). The second fluid is preferably in a different state from the first fluid--liquid-gas or gas-liquid combinations. However, the first and second fluids may be two different fluids in miscible in each other. The stable capillary microjet comprises a diameter d.sub.j at a given point A in the stream characterized by the formula: ##EQU1## wherein d.sub.j is the diameter of the stable microjet, = indicates approximately equally to where an acceptable margin of error is .+-.10%, .rho..sub.1 is the density of the liquid and .DELTA.P.sub.g is change in gas pressure of gas surrounding the stream at the point A.

Abstract: Devices, packaging and methodology for efficiently and repeatably creating aerosolized bursts of an analgesic (e.g., narcotic) containing formulation are disclosed. Devices are hand-held, self-contained units which are automatically actuated at the same release point in a patient's inspiratory flow cycle. The release point is automatically determined either mechanically or, more preferably calculated by a microprocessor which receives data from a sensor making it possible to determine inspiratory flow rate and inspiratory volume. The device is loaded with a cassette comprised of an outer housing which holds a package of individual disposable collapsible containers of an analgesic containing formulation for systemic delivery. Actuation of the device forces analgesic formulation through a porous membrane of the container which membrane has pores having a diameter in the range of about 0.25 to 3.0 microns, preferably 0.25 to 1.5 microns.

Abstract: Devices, packaging and methodology for efficiently and repeatably creating aerosolized bursts of an insulin containing formulation are disclosed. Devices are hand-held, self-contained units which are automatically actuated at the same release point in a patient's inspiratory flow cycle. The release point is automatically determined either mechanically or, more preferably calculated by a microprocessor which receives data from a sensor making it possible to determine inspiratory flow rate and inspiratory volume. The device is loaded with a cassette comprised of an outer housing which holds a package of individual disposable collapsible containers of an insulin containing formulation for systemic delivery. Actuation of the device forces insulin formulation through a porous membrane of the container which membrane has pores having a diameter in the range of about 0.25 to 3.0 microns, preferably 0.25 to 1.5 microns.

Abstract: The need for the delivery of insulin by injection can be reduced or eliminated by a method whereby an aerosolized insulin formulation is delivered to a patient's lungs and the rate at which the insulin is absorbed into the blood is increased by the use of an inhale-exhale breathing maneuver. Particles of insulin delivered to the surface of lung tissue will be absorbed into the circulatory system. The rate of absorption is enhanced by instructing the patient to inhale maximally and thereafter exhale maximally. This maneuver causes a spike in the rate at which insulin enters the circulatory system thereby increasing the rate at which glucose is removed from the circulatory system. The insulin may be a dry powder but is preferably in a liquid formulation delivered to the patient from a hand-held, self-contained device which automatically releases an aerosolized burst of formulation.

Abstract: A patient interface system for collecting and transferring data from a patient to a remote monitoring system, as well as methods for its use, are provided. The subject system uses: (a) a data collection device with a sensor and an interrogation device; (b) a processing device for processing the collected data; and (c) a communication device for transferring said collected data from the interface system to a remote monitoring system and receiving instructional data from a remote monitoring system. The subject system finds use in the remote monitoring of a variety of conditions, particularly in the remote monitoring of cardiac associated diseases. In addition, the sensor is a scale either programmed not to activate the patient interface system if it measures a weight below or above certain set weights or not to send measurements to the remote monitoring if it measures a weight below or above certain set weights.

Abstract: A nozzle comprised of a thin, flexible membrane material having a plurality of pores is disclosed. In one embodiment, the pores have an unflexed exit aperture diameter in the range of about 0.5 to about 2 microns (preferably about 1 micron) and are positioned substantially uniformly in the material, preferably about 50 microns apart. The nozzle preferably has a conical or trumpet-shaped cross-section. In another aspect of the invention, the exit aperture of the nozzle is surrounded by an elevated area protruding above the substantially planar exit side of the membrane in order to prevent intrusion of liquid back into the nozzle. The nozzle can be used to form an aerosol containing a pharmaceutical composition from the exit side of the nozzle upon forcible application of the composition to the entrance side of the nozzle. This aerosol can be used to administer the pharmaceutical composition, for example, to the eye or to a selected portion of the respiratory tract.

Abstract: The present invention provides a fastening method for fastening a first member to a second member by a bolt, comprising the steps of: inserting the bolt through a hole in the first member into a hole in the second member to start threadably engaging the bolt in a threaded hole provided in the second member; then, in a subsequent threadably engaging process, shaping, for example by plastically deforming or cutting, the holes of both the first and second members by a large-diameter portion provided around a bolt shank and having a diameter larger than that of the holes. The invention also provides a fastening system and a bolt used for the above-described method. With this method, it is possible to accurately connect the first and second members by the bolt, and to miniaturize the parts without increasing costs or lowering productivity.

Abstract: The need for the delivery of insulin by injection can be reduced or eliminated by delivering an aerosolized monomeric insulin formulation. Repeatability of dosing and more particularly the repeatability of the blood concentration versus time profile is improved relative to regular insulin. The blood concentration versus time profile is substantially unaffected by specific aspects of the patient's breathing maneuver at delivery. Further, the rate at which blood glucose is lowered is increased by the use of monomeric insulin. Particles of insulin and in particular monomeric insulin delivered to the surface of lung tissue will be absorbed into the circulatory system. The monomeric insulin may be a dry powder but is preferably in a liquid formulation delivered to the patient from a handheld, self-contained device which automatically releases an aerosolized burst of formulation.

Abstract: A method and apparatus to alter the shape of the cornea of an eye provides for heating a portion of the cornea to a temperature not exceeding the collagen shrinkage temperature, and applying a pressure differential to a portion of the cornea. The combined effect of elevated temperature and stretching forces leads to permanent residual strains in preferred directions, and thus to a permanent new shape of the cornea. The method is applicable to the correction or reduction of myopia, hyperopia, and astigmatism.

Abstract: A device for carrying equipment, such as a pair of snow skis and other ski equipment, is provided. The device comprises a container, a means for holding the skis attached to the outside surface of the container, and a carrying belt attached to the container. The device permits skis to be conveniently transported in a sling-like fashion. In addition, other supplies can be transported within the container, or secured to the outside of the container.

Abstract: A disposable package, tape, and cassette are provided which makes it possible to hold and disperse therefrom liquid, flowable formulations including aqueous formulations (solutions or dispersions with particles less than 0.25 microns in diameter) of a pharmaceutically active drug. In one embodiment formulation is packaged in individual dosage unit containers which containers are preferably interconnected. The package is designed to be integrated into a cassette which can be loaded into a dispersing device capable of individually opening dosage unit containers and aerosolizing the contents through a porous membrane, into a mouth piece on the cassette, for delivery to a patient. In addition to and alongside of each porous membrane, the package may include one or more openings through which air is forced in order to aid in avoiding the accumulation of aerosolized particles.

Abstract: A method of treating human patients is provided by the intrapulmonary delivery of a formulation containing a hematopoietic drug. The formulation is automatically released in an aerosolized form from a hand-held, self-contained, portable device comprised of a means for automatically releasing a measured amount of drug into the inspiratory flow path of a patient in response to information obtained from a means for measuring the inspiratory flow rate and determining the inspiratory volume of a patient. Reproducible dosing is obtained by providing for automatic release at the same inspiratory flow rate and inspiratory volume each time drug is released. The device includes a timer to enable a patient to take a drug at the same time each day. Further, overadministration of a hematopoietic drug formulation is avoided by providing a pre-programmed microprocessor designed to avoid overdosing.

Abstract: The activation of neurons in specific areas of a mammalian brain are determined by measurement of levels of mRNA following administration of an agent that potentially affects neuronal activity. Differential levels of mRNA caused by an agent can be measured, as can the specific distribution of the alteration of neuronal activity. Many mental disorders are associated with the abnormal function of a particular area of the brain. The present invention allows the determination of which area of the brain, if any, is affected by an administered agent. Accordingly, the invention provides a valuable tool for assaying compounds as potential therapeutic agents.

Abstract: A method of determining the probability of an in vitro fertilization (IVF) or embryo transfer (ET) method being successful is disclosed. Relaxin can be measured directly in the serum or indirectly by culturing granulosa lutein cells extracted from the patient as part of an IVF/ET procedure. A method of enhancing the rate of a successful pregnancy resulting from an IVF/ET procedure is also disclosed whereby relaxin is administered.

Abstract: A method of concentrating a disease-related conformation of a protein such as the PrP.sup.Sc in a sample is disclosed. The method comprises liquefying the sample and adding a complexing agent such as phosphotungstic acid (PTA) which complexes preferentially or exclusively with the PrP.sup.Sc. After the complex is formed the composition is centrifuged until the complex settles at the bottom. Thereafter, the supernatant is poured away. The remaining pellet may be resuspended in an aqueous solution containing a protease inhibitor for storage. The PTA stains the PrP.sup.Sc making the resulting concentrated PrP.sup.Sc susceptible to further analysis, making it possible to quickly and efficiently determine the presence of PrP.sup.Sc and its concentration in a sample. The method can be used to render a sample non-infectious by removing all or substantial of the infectious form of a protein from a sample.

Abstract: The need for the delivery of insulin by injection can be reduced or eliminated by a method whereby an aerosolized insulin formulation is delivered to a patient's lungs and the rate at which the insulin is absorbed into the blood is increased by the use of monomeric insulin and/or an inhale-exhale breathing maneuver. Particles of insulin and in particular monomeric insulin delivered to the surface of lung tissue will be absorbed into the circulatory system. The rate of absorption is enhanced by the monomeric form of insulin and by instructing the patient to inhale maximally and thereafter exhale maximally. This maneuver causes a spike in the rate at which insulin enters the circulatory system thereby increasing the rate at which glucose is removed from the circulatory system. The insulin or insulin analog may be a dry powder but is preferably in a liquid formulation delivered to the patient from a hand-held, self-contained device which automatically releases an aerosolized burst of formulation.

Abstract: A method of treating human patients is provided by the intrapulmonary delivery of a pharmaceutically active peptide formulation. The formulation is automatically released in an aerosolized form from a hand-held, self-contained, portable device comprised of a means for automatically releasing a measured amount of drug into the inspiratory flow path of a patient in response to information obtained from a means for measuring the inspiratory flow rate and determining the inspiratory volume of a patient. Reproducible dosing is obtained by providing for automatic release at the same inspiratory flow rate and inspiratory volume each time drug is released. The device includes a timer to enable a patient to take a drug at the same time each day. Further, overadministration of hormone formulations is avoided by providing a pre-programmed microprocessor designed to avoid overdosing.

Abstract: A protein designated Prion Protein Modulator Factor (PPMF) is disclosed which protein is an auxiliary factor in prion replication. PPMF is primarily characterized by its ability to bind to PrP.sup.C and facilitate a conformational change from PrP.sup.C to PrP.sup.Sc. A discontinuous epitope on PrP.sup.C comprising residues 172, 215 and 219 of human PrP.sup.C binds PPMF which is encoded by a nucleotide sequence derived from an organism selected from the group consisting of cow, sheep, mouse, hamster and human. In converting PrP.sup.C to PrP.sup.Sc the PPMF forms a PrP.sup.C /PrP.sup.Sc complex and is a rate limiting compound in the formation of that complex. Molecules, including antibodies, which bind PPMF or its epitope on PrP.sup.C are useful in the treatment of prion disease. Pharmacophores of the PrP.sup.C epitope are disclosed as are useful therapeutics and pharmacophores of the PPMF surface which binds PrP.sup.C. Animals resistant to prion disease are taught as are genes for producing such animals.

Abstract: Devices, packaging and methodology for creating aerosols are provided which allow for efficient and repeatable delivery of drugs to the lungs of a patient. Devices are hand-held, self-contained units which are automatically actuated at the same release point in a patient's inspiratory flow cycle. The release point is calculated by a microprocessor which receives data from a sensor making it possible to determine inspiratory flow rate and inspiratory volume. The device is loaded with a cassette comprised of an outer housing which holds a package of individual collapsible containers of pharmaceutically active drug. Actuation of the device forces drug through a porous membrane of the container which membrane has pores having a diameter in the range of about 0.25 to 6.0 microns. The porous membrane is positioned in alignment with a surface of a channel through which a patient inhales air.