Evidence for opioid variability, Part 1: A biological perspective.

The interplay of biological and pyschosocial factors explain the unique individual differences in opioid requirements that occur among postoperative patients. Nurses must be familiar with the physiologic mechanisms that influence opioid analgesia. Despite growing evidence that doses of opioid analgesics needed to achieve pain relief vary significantly from patient to patient, standardized dosing regimens continue to drive administration of medications for postoperative pain. In this article, evidence-based literature related to the biologic factors that contribute to differences in responses to opioid medication will be examined. Content will assist the Perioperative Nurse to recognize the pharmacology of opioid analgesics and the scientific basis for differences in the body's ability to metabolize and excrete opioids. These differences include age, gender, genetic predisposition, type of surgical procedure, preexisting pain, and prior or concurrent opioid use. Specific terms are introduced and defined to increase understanding of opioid variability.

Evidence for opioid variability, Part 2: Psychosocial influences.

There is substantial evidence to show that certain biological and psychosocial factors affect opioid requirements after surgery. In fact, evidence suggests that individuals are much more likely to be different rather than similar in how they sense pain, react to it and respond to therapy. In an earlier report (Seminars in Perioperative Nursing 10:3-16, 2001), we examined research related to the biological differences that explain variability in postoperative opioid use and defined relevant terminology. Here, we discuss the evidence that links psychosocial experiences to postoperative analgesic outcomes and pain, which include psychological states of patients, cultural influences and attitudes, and beliefs and biases held by both patients and health professionals. Content will assist perioperative nurses to understand the characteristics of their patients and circumstances that place patients at risk for needing increased analgesia or experiencing poor pain control. As perioperative nurses strive to integrate research into practice, it will be important to examine the results of research studies and to determine the usefulness of this information in developing individualized plans for postoperative pain management.

Genome-wide, large-scale production of mutant mice by ENU mutagenesis.

In the post-genome era, the mouse will have a major role as a model system for functional genome analysis. This requires a large number of mutants similar to the collections available from other model organisms such as Drosophila melanogaster and Caenorhabditis elegans. Here we report on a systematic, genome-wide, mutagenesis screen in mice. As part of the German Human Genome Project, we have undertaken a large-scale ENU-mutagenesis screen for dominant mutations and a limited screen for recessive mutations. In screening over 14,000 mice for a large number of clinically relevant parameters, we recovered 182 mouse mutants for a variety of phenotypes. In addition, 247 variant mouse mutants are currently in genetic confirmation testing and will result in additional new mutant lines. This mutagenesis screen, along with the screen described in the accompanying paper, leads to a significant increase in the number of mouse models available to the scientific community. Our mutant lines are freely accessible to non-commercial users (for information, see http://www.gsf.de/ieg/groups/enu-mouse.html).

MouseNet database: digital management of a large-scale mutagenesis project.

The Munich ENU Mouse Mutagenesis Screen is a large-scale mutant production, phenotyping, and mapping project. It encompasses two animal breeding facilities and a number of screening groups located in the general area of Munich. A central database is required to manage and process the immense amount of data generated by the mutagenesis project. This database, which we named MouseNet(c), runs on a Sybase platform and will finally store and process all data from the entire project. In addition, the system comprises a portfolio of functions needed to support the workflow management of the core facility and the screening groups. MouseNet(c) will make all of the data available to the participating screening groups, and later to the international scientific community. MouseNet(c) will consist of three major software components:* Animal Management System (AMS)* Sample Tracking System (STS)* Result Documentation System (RDS)MouseNet(c) provides the following major advantages:* being accessible from different client platforms via the Internet* being a full-featured multi-user system (including access restriction and data locking mechanisms)* relying on a professional RDBMS (relational database management system) which runs on a UNIX server platform* supplying workflow functions and a variety of plausibility checks.

Fast magic-angle spinning proton NMR studies of polymers at surfaces and interfaces.

Solid-state proton NMR with fast magic-angle sample spinning has been used to study the structure and dynamics of polymers and the water interface in porous glass composites. The composites were prepared by photopolymerization of poly(ethyl acrylate) and other acrylate formulations in a high surface-area rigid glass matrix with 40-A interconnected pores. High resolution solid-state proton spectra were obtained for polymer films and composites with 15 kHz magic-angle sample spinning at temperatures above the polymer glass transition temperature. The solid-state proton spectra can be detected with high sensitivity and used to determine the composition of polymer and water filling the pores. These results and spin diffusion studies using 1H-29Si 2D heteronuclear correlation and wideline separation NMR show that the polymer fills the central 30 A of the pore, and that the remaining volume is filled with surface hydroxyl groups and water.

Glycoprotein gp50-negative pseudorabies virus: a novel approach toward a nonspreading live herpesvirus vaccine.

Essential herpesvirus glycoproteins are involved in membrane fusion processes during infection, e.g., viral penetration and direct cell-to-cell transmission. We previously showed that the gD-homologous glycoprotein gp50 of pseudorabies virus (PrV) is essential for virus entry into target cells but proved to be dispensable for direct viral cell-to-cell spread in cell culture (I. Rauh and T. C. Mettenleiter, J. Virol. 65:5348-5456, 1991). For gp50-negative (gp50-) viruses, after phenotypic complementation necessary for primary infection, the only means of viral spread is by way of direct cell-to-cell transmission. In contrast, virus mutants lacking the essential gB-homologous glycoprotein gII after phenotypic complementation are only able to infect primary target cells and are blocked in further viral spread. To analyze how these in vitro phenotypes translate into virus replication in the animal, mice were infected intranasally with gp50- or gII- PrV mutants after prior phenotypic complementation by propagation on cell lines providing the essential glycoprotein in trans. Our results show that whereas the gII- mutants did not cause disease or any symptoms, gp50- mutants derived from two different PrV strains were fully virulent, with animals exhibiting severe symptoms ultimately leading to death. However, free infectious virus could not be recovered from either gp50- or gII- PrV-infected animals. We conclude that direct cell-to-cell transmission as the only means of viral spread of the gp50- mutants is sufficient for a full virulent phenotype in mice. After infection of pigs with phenotypically complemented gp50- PrV, only mild symptoms were observed, whereas the gII- mutant was totally avirulent. In both cases, shedding of infectious virus did not occur, in contrast to results with animals infected by gX- PrV that showed severe signs of disease and extensive virus shedding. After challenge infection with the highly virulent NIA-3 strain, the previously gII- PrV-infected animals exhibited severe symptoms, whereas the gp50- PrV-infected pigs showed a significant level of protection. In conclusion, vaccination with a PrV mutant lacking glycoprotein gp50, which is unable to spread between animals because of a lack of formation of free infectious virions, can confer on pigs protection against challenge infection. These results provide the basis for the development of new, nonspreading live herpesvirus vaccines based on gp50- PrV mutants.

Effect of exercise conditioning on red blood cell volume and erythropoietin concentration in the beagle dog.

To determine if endurance conditioning has a stimulating effect on red blood cell and erythropoietin production, we exercised five beagle dogs on a motor-driven treadmill for 1 hour per day, 5 days per week, for 6 weeks at a speed near their maximal capability. Three additional beagles were kept in cages and served as nonconditioned controls. Endurance conditioning in these dogs produced no increase in red blood cell mass, serum erythropoietin concentration, or any other blood cell index measured. We conclude that this type of exercise conditioning does not produce the necessary stimulus for an increase in erythropoiesis.