A menu driven reprogrammable drug pump is provided with a memory, such as flash memory, a display, a keyboard, and a communications port to allow a generic pump to be programmed with a desired pump application (therapy) program and patient specific settings. Programming and data transfer with another pump or a computer to and from the patient pump is by the communications port that allows local and/or remote communications with the pump. Flash memory stores the pump application program during use. Patient safety is provided by a cassette identification system, an occlusion detection system, and a latch/lock detection system. Automated testing of the pump is by a closed loop testing system.

Drug pump systems and methods

Toll-like receptor 4 (TLR4) is activated by lipopolysaccharide (LPS), a component of Gram-negative bacteria to induce production of pro-inflammatory mediators aiming at eradication of the bacteria. Dysregulation of the host responses to LPS can lead to a systemic inflammatory condition named sepsis. In a typical scenario, activation of TLR4 is preceded by binding of LPS to CD14 protein anchored in cholesterol- and sphingolipid-rich microdomains of the plasma membrane called rafts. CD14 then transfers the LPS to the TLR4/MD-2 complex which dimerizes and triggers MyD88- and TRIF-dependent production of pro-inflammatory cytokines and type I interferons. The TRIF-dependent signaling is linked with endocytosis of the activated TLR4, which is controlled by CD14. In addition to CD14, other raft proteins like Lyn tyrosine kinase of the Src family, acid sphingomyelinase, CD44, Hsp70, and CD36 participate in the TLR4 signaling triggered by LPS and non-microbial endogenous ligands. In this review, we summarize the current state of the knowledge on the involvement of rafts in TLR4 signaling, with an emphasis on how the raft proteins regulate the TLR4 signaling pathways. CD14-bearing rafts, and possibly CD36-rich rafts, are believed to be preferred sites of the assembly of a multimolecular complex which mediates the endocytosis of activated TLR4.

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Co-operation of TLR4 and raft proteins in LPS-induced pro-inflammatory signaling

Vastly stimulated by the discovery of opioid receptors in the early 1970s, preclinical and clinical research was directed at the study of stereoselective neuronal actions of opioids, especially those played in their crucial analgesic role. However, during the past decade, a new appreciation of the non-neuronal actions of opioids has emerged from preclinical research, with specific appreciation for the nonclassic and nonstereoselective sites of action. Opioid activity at Toll-like receptors, newly recognized innate immune pattern recognition receptors, adds substantially to this unfolding story. It is now apparent from molecular and rodent data that these newly identified signaling events significantly modify the pharmacodynamics of opioids by eliciting proinflammatory reactivity from glia, the immunocompetent cells of the central nervous system. These central immune signaling events, including the release of cytokines and chemokines and the associated disruption of glutamate homeostasis, cause elevated neuronal excitability, which subsequently decreases opioid analgesic efficacy and leads to heightened pain states. This review will examine the current preclinical literature of opioid-induced central immune signaling mediated by classic and nonclassic opioid receptors. A unification of the preclinical pharmacology, neuroscience, and immunology of opioids now provides new insights into common mechanisms of chronic pain, naive tolerance, analgesic tolerance, opioid-induced hyperalgesia, and allodynia. Novel pharmacological targets for future drug development are discussed in the hope that disease-modifying chronic pain treatments arising from the appreciation of opioid-induced central immune signaling may become practical.

/pdf/exploring-the-neuroimmunopharmacology-of-opioids-an-4aubuxv8sa.pdf

Exploring the Neuroimmunopharmacology of Opioids: An Integrative Review of Mechanisms of Central Immune Signaling and Their Implications for Opioid Analgesia

An infusion device with a disposable administration set which is inexpensive to manufacture. In the preferred embodiment of the present invention the disposable administration set has a plurality of elongated cam followers connected to a plate assembly, wherein the cam followers are displaced in a predetermined sequence and forced against a delivery tube by cam means driven by rotary drive means. The disposable administration set is injection molded as a single integral piece. The disposable administration set includes adjustment spacers disposed between the plate assembly and the cam followers which adjust the distance between them to keep the device accurate. In the preferred embodiment of the present invention the cam means are configured to provide fluid delivery at a consistent and uniform rate.

Infusion device with disposable elements

A microelectronic connection component includes a dielectric sheet having an area array of elongated, strip-like leads. Each lead has a terminal end fastened to the sheet and a tip end detachable from the sheet. Each lead extends horizontally parallel to the sheet, from its terminal end to its tip end. The tip ends are attached to a second element, such as another dielectric sheet or a semiconductor wafer. The first and second elements are then moved relative to one another to advance the tip end of each lead vertically away from the dielectric sheet and deform the leads into a bent, vertically extensive configuration. The preferred structures provide semiconductor chip assemblies with a planar area array of contacts on the chip, an array of terminals on the sheet positioned so that each terminal is substantially over the corresponding contact, and an array of metal S-shaped ribbons connected between the terminals and contacts. A compliant dielectric material may be provided between the sheet and chip, substantially surrounding the S-shaped ribbons.

Microelectronic mounting with multiple lead deformation and bonding

A Hall sensing apparatus having a large dynamic range is adapted for generating a current signal substantially in phase with the current in a conductor. The Hall sensing apparatus has a magnetic field concentrator assembly with oppositely disposed pick-up plates, each with a centrally attached concentrator rod for being symmetrically positioned on either side of the conductor. A Hall sensor element is wholly positioned in the space between the ends of the rods remote from the plates. A current circuit, having an externally controlled current varying device and temperature drift control device in series with a current source, provides a Hall current through the sensor element. A detection circuit, coupled across the width of the sensor element, provides an inverted and non-inverted signal in phase with the conductor current which are coupled to the inverting input of a summing amplifier. A reference voltage is then coupled to the non-inverting input of the summing amplifier to generate a dc bias offset control signal which is coupled, in a negative feedback configuration, to control the Hall current and thereby decrease the dc offset bias.

Hall sensing apparatus

A portable phase angle meter instrument for use on electric utility power distribution systems. A portable phase angle meter instrument is interconnected between two distribution conductors to generate a voltage signal and current signal substantially in phase with the voltage across the conductors and the current in one of the conductors respectively. A potential probe with a conductive hook for interconnection to a first conductor, houses a first capacitor. A current probe assembly housing a second capacitor, has a head for interconnection to a reference conductor. The head has a Hall sensor or a transformer sensor for generating a current signal substantially in phase with the reference conductor current, and a plate for making electrical contact with the reference conductor. The capacitors are interconnected in series between the plate and the hook via a high voltage cable. Circuitry in a housing attached to the current probe is coupled between the second capacitor and the plate for generating a voltage signal substantially in phase with the voltage between the conductors. The current and voltage signals are digitized and processed to generate a lead signal when the current leads the voltage and a lag signal when the current lags the voltage. Registers accumulate counts of clock pulses of the lead and lag signals and the total number of clock pulses which occur during a selected period of time. Phase angle is calculated from the accumulated counts in the registers.

Portable phase angle meter instrument

A static junction seal assembly for electrically insulating a high potential between the interior and the exterior of a housing. The housing has first and second halves, having a first seal surface and a second seal surface, respectively. The seal surfaces are covered with a dielectric grease and are juxtaposed with a non-conductive gasket therebetween. The space between the seal surfaces increases from a central location to an edge location and the gasket adjacent the central location has a maximum thickness which decreases continuously from the central location to a gasket edge location when the gasket and seal surfaces are juxtaposed in an uncompressed state. The relative configuration of the first and second seal surfaces and the gasket are thus selected so that as the gasket is progressively compressed between the seal surfaces, a gasket bulge will initially form at the central location and thereafter move from the central location to the edge location. The movement of the gasket bulge displaces and expels the grease and any entrapped air along the seal surface to form a grease filled, bubble free, insulating seal. For sealing an access port through the housing, the port is provided with sides sloped inwardly toward the center of the port at a first angle. A plug having inwardly sloped sides at a second smaller angle is inserted in the port and is compressed thereby progressively forming a plug bulge which moves progressively upward expelling grease and all entrapped air.

Harry P. Levin

Papers

Hall sensing apparatus

Portable phase angle meter instrument

Electrically insulating seal assembly