Intractable pruritus during outpatient epidural hydromorphone infusion: a case report and a focused review of the literature.

BACKGROUND: Intraspinal drug delivery therapy has been increasingly used in patients with intractable, nonmalignant pain who have failed to respond to conventional treatment or cannot tolerate systemic opioid(s) due to adverse events. By infusing a small dose of an opioid analgesic directly into the cerebrospinal fluid, near opioid receptors, profound spinal analgesia can be obtained. Before the implantation of permanent intraspinal pump, a neuraxial opioid infusion trial is usually conducted to demonstrate the effectiveness of neuraxial opioid for analgesia. Patient-controlled epidural opioid infusion trial, performed in an outpatient setting, is one of the approaches used to conduct such a trial. OBJECTIVE: To report a case of severe pruritus observed during the continuous epidural hydromorphone infusion trial and to conduct a focused review of the literature. CASE REPORT: An otherwise healthy 56-year-old lady, with a 4-year history of severe low back pain and bilateral leg pain due to failed back surgery syndrome, was referred to our clinic for intraspinal drug delivery therapy. Following a preimplantation psychological evaluation confirming her candidacy, she consented to an outpatient patient-controlled continuous epidural hydromorphone trial. A tunneled lumbar epidural catheter was placed at L3-L4 with catheter tip advanced to L2 under fluoroscopic guidance. Satisfactory catheter placement was confirmed by epidurogram. The catheter was then tunneled subcutaneously and connected to a Microject™ patient-controlled epidural analgesia (PCEA) pump (Codman, Raynham, MA). The pump was programmed to deliver hydromorphone 0.3 mL/h (0.06 mg, concentration 0.2 mg/mL) at basal rate of 0.3 mL/h, with bolus dose set at 0.2 mL (0.04 mg) and 30-minute lockout interval. The patient was instructed how to operate the infusion pump prior to discharging home. During the infusion trial, she reported satisfactory analgesia (>90 percent pain reduction) and was able to reduce her oral opioid dose by more than 80 percent. However, she developed severe, persistent itching, unresponsive to meticulous epidural infusion titration or various antipruritic treatments. Her pruritus remained severe and unabated until a few hours after the termination of the epidural hydromorphone infusion. CONCLUSION: Pruritus may occur and persist during epidural hydromorphone infusion. This report describes severe pruritus in a patient on epidural hydromorphone administration, in the setting of an outpatient infusion trial.

Surface engineering of microparticles by novel protein transfer for targeted antigen/drug delivery.

Biodegradable microparticles can function as an adjuvant by targeting antigens to professional antigen presenting cells such as dendritic cells and macrophages. To enhance targeting of microparticles, we have developed a novel method of attaching immunostimulatory molecules such as B7-1 to the surface of albumin microparticles utilizing the glycosylphosphatidyl inositol (GPI) anchor. GPI-B7-1 attaches to the surface of albumin microparticles in a protein transfer mediated process and is functionally active. This protein transfer was dependent on the concentration of the GPI-anchored protein, and independent of temperature and incubation time. Results show that the binding of the GPI-anchored protein is specifically occurring through an interaction between the GPI-anchor and the albumin microparticle surface. Stability studies indicate that the GPI-anchored protein can remain attached to the surface of the microparticle up to 7 days, with storage at 4 degrees C providing the optimal stability. Finally, we were able to simultaneously attach two different GPI-anchored proteins, GPI-B7-1 and GPI-ICAM-1, to the microparticles, demonstrating the capability of attaching more than one GPI-anchored protein to the microparticle surface. This novel method of attaching proteins to the surface of microparticles has potential implications in using microparticles as an antigen delivery device in vaccines as well as in targeted drug delivery.

Using the humanities to strengthen the concept of professionalism among first-professional year pharmacy students.

OBJECTIVES: To engage pharmacy students at the McWhorter School of Pharmacy in an authentic discussion of professionalism early in their education. METHODS: A booklet was prepared that included several classic short stories and essays that dealt with professionalism. This booklet was sent to all entering students in the class of 2008 and 2009 during the summer prior to their first-professional year of the PharmD program. The stories and essays were discussed in small groups with faculty facilitation during orientation when the students first arrived on campus. A survey instrument was created and administered to assess the impact of this innovative approach to enhancing professionalism. RESULTS: The program was well received and engaged our pharmacy students in a productive discussion on professionalism. Both classes' mean scores on survey items related that the students were engaged in the discussion of professionalism. Survey results pertaining to professional behavior also indicated increased awareness of the importance of professionalism. CONCLUSION: Enhancing professionalism requires a culture change that necessitates addressing professionalism at its core, a calling to serve, in a persistent and continual manner. Requiring students to read and think about professionalism in a novel way, before they even begin their first-professional year of pharmacy school, appears to be an effective approach to nurturing/encouraging professionalism.

Modified cell ELISA to determine the solubilization of cell surface proteins: Applications in GPI-anchored protein purification.

A major step in purifying membrane bound proteins involves the solubilization of the protein of interest from the cell membranes. Glycosylphosphatidyl inositol (GPI)-anchored proteins pose a singular problem in this solubilization step since they are found in detergent-resistant membrane complexes and accordingly are insoluble in cold Triton X-100. In this study we have developed a modified cell ELISA that determines the solubility of these cell surface proteins under various solubilization conditions. Using this non-radioactive method we show that the combination of saponin/Triton X-100 at 4 degrees C solubilized GPI-anchored proteins more efficiently than Triton X-100 at 4 degrees C. The combination of saponin/Triton X-100 at 4 degrees C avoids the potential of activating proteases that occurs when using Triton X-100 at 37 degrees C. Furthermore, our method also shows the saponin/Triton X-100 solubilized GPI-anchored proteins equivalent to the more expensive octyl beta-glucoside. This is a particularly important consideration in large-scale protein purification. This method obviates the need to use radioactivity, gel electrophoresis and immunoblotting procedures. The solubilization conditions determined by this modified ELISA are readily translated to the practical application of large-scale protein purification as demonstrated in the purification of two different recombinant GPI-anchored proteins, GPI-hB7-1 (CD80) and GPI-mICAM-1 (CD54).