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Biomedical subjects

R Shane

Publications and source records attributed to R Shane.

At least 19 recordsLinked to original sources

Analgesia elicited by OFQ/nociceptin and its fragments from the amygdala in rats.

The heptadecapeptide, orphanin FQ/nociceptin (OFQ/N), binds with high affinity to the ORL-1/KOR-3 opioid receptor clone, yet binds poorly with traditional opioid receptors. OFQ/N has a complex functional profile with relation to nociceptive processing, displaying pro-nociceptive properties in some studies, acting as an inhibitor of stress-induced analgesia in others, yet producing both spinal and supraspinal antinociceptive actions in other studies. Among the intracerebral sites at which OFQ/N might produce one or more of these actions is the amygdala which has been intimately implicated in both antinociceptive and stress-related responses. Therefore, the present study assessed whether microinjections into the amygdala of equimolar doses of OFQ/N(1-17) or its shorter-chained active fragments, OFQ/N(1-11) or OFQ/N(1-7), would produce analgesia as measured by either reactivity to high-intensity radiant heat or reactivity to electric shock, and produce hyperalgesia as measured by reactivity to lower-intensity radiant heat. OFQ/N(1-17) in the amygdala produced a dose-dependent and time-dependent increase in high-intensity tail-flick latencies with maximal effects observed at a dose range of 0.75-3 nmol, and lesser effects at lower (0.015-0.15 nmol) and higher (5.5-30 nmol) doses. Both OFQ/N(1-11) and OFQ/N(1-7) in the amygdala displayed lower magnitudes of analgesia than OFQ/N(1-17) on this measure, with OFQ/N(1-11) displaying maximal effects at higher (15-30 nmol) doses and OFQ/N(1-7) displaying maximal effects at lower (0.15-1.5 nmol) doses. In contrast to traditional mu and kappa opioids and beta-endorphin, none of the OFQ/N fragments in the amygdala exhibited any analgesic responses on the jump test. Finally, using a low-intensity radiant heat assay capable of detecting hyperalgesic responses, each of the OFQ/N fragments in the amygdala increased tail-flick latencies on this measure. Therefore, OFQ/N fragments appear to exert only analgesic responses in the amygdala with quantitative and qualitative differences relative to traditional opioid agonists.

Amygdala↗

Modulation of endomorphin-2-induced analgesia by dipeptidyl peptidase IV.

The tetrapeptide, endomorphin-2 (Tyr-Pro-Phe-PheNH2) possesses high affinity for mu opioid receptors, and produces potent analgesia in mice. Its structure appears to satisfy the substrate requirements of the proteinase, dipeptidyl peptidase IV which removes dipeptides from the amino terminus of peptides containing proline as the penultimate amino acid. A potent, stable and specific inhibitor of this enzyme, Ala-Pyrrolidonyl-2-nitrile, has been described which should potentiate endomorphin-2-induced analgesia. Further, since dipeptidyl peptidase IV has an absolute requirement for l-Pro, a more metabolically-stable d-Pro2-endomorphin-2 analog should produce longer analgesic actions at lower doses. The present study found that endomorphin-2 was degraded approximately twice as fast than the chromogenic substrate, Ala-Pro-2naphthylamide, by dipeptidyl peptidase IV, whereas d-Pro2-endomorphin-2 was totally resistant to this enzyme's action. d-Pro2-endomorphin-2 (ED50=0.05 microg) was more potent than endomorphin-2 (ED50=30 microg) in significantly increasing tail-flick latencies with longer durations of action. Both the peptide and analogue were equipotent (ED50=0.5 microg) in significantly increasing jump thresholds. Ala-Pyrrolidonyl-2-nitrile (10-75 nmol) elicited a dose-dependent analgesia, and potentiated the analgesic actions of endomorphin-2, particularly on the tail-flick test. Whereas systemic naltrexone (2.5, 10 mg/kg) dose-dependently eliminated each of the three forms of analgesia on the jump test as well as the peak (15 min) effect on the tail-flick test, analgesia elicited by either endomorphin-2, d-Pro2-endomorphin-2 or Ala-Pyrrolidonyl-2-nitrile returned after 30-60 min in naltrexone-treated rats on the tail-flick test. These data strongly suggest that dipeptidyl peptidase IV plays a role in the inactivation of endomorphin-2 in vivo, and thereby modulates its central analgesic actions.

Analgesics, Opioid↗

The three dimensions of managed care pharmacy practice.

Our goal is to provide a framework for pharmacy in an evolving healthcare marketplace by identifying and discussing the three dimensions of pharmacy practice: (1) pharmacy practice across the continuum of care; (2) the major elements of pharmacy practice; and (3) the evolution of pharmacy during the five stages of the development of managed care. The framework was devised under the proposition that there is a substantial consistency in what patients need or should expect from pharmacists. As integrated health systems develop, pharmacists must apply their skills and knowledge across the continuum of care to ensure that they play an integral part in the systems. In a managed care environment characterized by change and the development of integrated health systems, pharmacists have opportunities to become involved directly in patient care in such areas as disease prevention, home healthcare, primary care, and subacute care. Information systems, hospital drug distribution, clinical pharmacy, and the fiscal environment comprise the major elements of pharmacy practice within an integrated health system, and the way in which each of these elements evolves as the healthcare market adapts to managed care is critical to pharmacy practice. If the pharmacy profession can demonstrate its ability to manage disease and health, improve outcomes, and reduce costs within the evolving healthcare system, pharmacists will play a vital role in the managed healthcare market in the approaching new millennium.

Continuity of Patient Care↗

Use of critical pathways and indicators in pharmacy practice.

The development of critical pathways along with continuous quality improvement and patient-focused care represents one of the key initiatives in health care in the 1990s. The critical pathway defines the components of care, including treatments, diagnostic measures, and activities to be performed each day, to achieve the desired outcome for a patient with a given diagnosis. Indicators can then be used to define opportunities for improving the pathway. Participation in the critical pathway development process provides pharmacists with an opportunity to utilize their expertise in the medication use process to ensure optimal medication management.

Clinical Protocols↗

A team approach to adverse drug reaction surveillance: success at a tertiary care hospital.

A retrospective adverse drug reaction (ADR) reporting system has been in place at Cedars-Sinai Medical Center for 7 years. Initially, the system identified 300 to 400 ADRs per year. After adding a checklist, that number increased to 750 to 850 per year, an ADR rate of about 2% of total patient admissions. To increase the ADR reporting rate, we initiated a concurrent surveillance program in conjunction with the retrospective system. In the first year of the program, the combined systems identified 1,174 ADRs. In addition, the ADR rate per 100 patient days increased to between 0.5 and 0.7, and the ADR per admission rate increased to 4%. As a result of the more effective ADR surveillance program, the P & T Committee has additional data from which to develop guidelines and educational programs to increase ADR awareness and prevention, and thus, to improve patient outcomes.

Adverse Drug Reaction Reporting Systems↗

A stepwise approach to the evaluation and selection of a hospital pharmacy information system.

The current demands for cost reduction, increased efficiency, and quality care placed upon hospital pharmacy departments underscores the need for an effective information system. In this article, we describe the stepwise approach we used to evaluate and select a new pharmacy information system. The importance of involving staff in the evaluation process is discussed, along with the mechanisms we used to learn as much as we could about the vendors before making our selection.

Clinical Pharmacy Information Systems↗