Evidence for nociceptin/orphanin FQ (NOP) but not µ (MOP), δ (DOP) or κ (KOP) opioid receptor mRNA in whole human blood.

BACKGROUND: While it is well known that opioids depress the immune system, the site(s) of action for this depression is highly controversial. Immune modulation could occur directly at the immune cell or centrally via the hypothalamic-pituitary-adrenal axis. In a number of studies using individual enriched immune cell populations we have failed to detect classical µ (MOP), δ (DOP) and κ (KOP) receptors. The non-classical nociceptin/orphanin FQ (N/OFQ) receptor (NOP) is expressed on all cells examined thus far. Our hypothesis was that immune cells do not express classical opioid receptors and that using whole blood would definitively answer this question. METHODS: Whole blood (containing all immune cell types) was incubated with opioids (morphine and fentanyl) commonly encountered in anaesthesia and with agents mimicking sepsis [lipopolysaccharide (LPS) and peptidoglycan G (PepG)]. Opioid receptor mRNA expression was assessed by endpoint polymerase chain reaction (PCR) with gel visualisation and quantitative PCR. RESULTS: Classical MOP, DOP, and KOP receptors were not detected in any of the samples tested either at rest or when challenged with opioids, LPS or PepG. Commercial primers for DOP did not perform well in quantitative PCR, so the absence of expression was confirmed using a traditional gel-based approach. NOP receptors were detected in all samples; expression was unaffected by opioids and reduced by LPS/PepG combinations. CONCLUSIONS: Classical opioid receptors are not expressed on circulating immune cells.

Opioids and immune modulation: more questions than answers.

Opioid addicts are more likely to present with infections suggesting opioids are immune modulators. The potential sites/mechanism(s) for this modulation are controversial and on close inspection not well supported by the current literature. It has long been assumed that opioid-induced immune modulation occurs via a combination of direct actions on the immune cell itself, via the hypothalamic-pituitary-adrenal (HPA) axis, or both. Opioid receptors are classified as MOP (µ, mu), DOP (δ, delta), and KOP (κ, kappa)--classical naloxone sensitive receptors--or NOP (the receptor for nociceptin/orphanin FQ), which is naloxone insensitive. Opioids currently used in clinical practice predominantly target the MOP receptor. There do not appear to be classical opioid receptors present on immune cells. The evidence for HPA activation is also poor and shows some species dependence. Most opioids used clinically or as drugs of abuse do not target the NOP receptor. Other possible target sites for immune modulation include the sympathetic nervous system and central sites. We are currently unable to accurately define the cellular target for immune modulation and suggest further investigation is required. Based on the differences observed when comparing studies in laboratory animals and those performed in humans we suggest that further studies in the clinical setting are needed.

Reproducibility and validity of radiographically determined gastrointestinal and segmental colonic transit times in spinal cord-injured patients.

BACKGROUND: Total gastrointestinal transit times (GITT) and segmental colonic transit times (CTT) are commonly used to describe bowel function in individuals with spinal cord injury (SCI). STUDY DESIGN: Reproducibility study. OBJECTIVES: To describe inter- and intrasubjective as well as interobserver variations in GITT and segmental CTT in patients with SCI. Furthermore, to study associations between GITT or segmental CTT and colorectal symptoms. SETTING: Spinal Cord Unit, Viborg Hospital, Denmark. METHODS: Thirty SCI patients took 10 radio-opaque markers on 6 consecutive days and an abdominal X-ray was taken on day 7. The same procedure was repeated after 3 months. GITT and CTT were computed from the number of markers in the entire colorectum and in the left and the right colon. Intra- and interobserver variations were described as dispersion (numerical difference/mean). RESULTS: Intersubjective variation was large for GITT (range: 0.6-6.3 days), right CTT (range: 0.1-5.5 days) and left CTT (range: 0-4.9 days). Intrasubjective variation was acceptable for GITT (dispersion: 0.28) but less good for right (dispersion: 0.63) and left CTT (dispersion: 0.68). Interobserver variation was very small. No correlations were found between GITT, right or left CTT and colorectal symptoms. CONCLUSION: GITT and right and left CTT are of limited value for clinical decision-making in individual patients but may be useful for comparison of groups of patients with SCI.

A comparison of spreader penetration depth and load required during lateral condensation in teeth prepared using various root canal preparation techniques.

AIM: To compare the influence of various root canal preparation techniques on spreader penetration depth and load required during lateral condensation with gutta-percha and sealer. METHODOLOGY: Eighty extracted human teeth with single and straight canals were used. Twenty teeth were instrumented using one of four root canal preparation techniques. The four preparation techniques were: step-back technique without Gates-Glidden drills, step-back technique with Gates-Glidden drills, crown-down pressureless technique and hybrid technique (step-down/step-back). After root canal preparation had been completed a simulated periodontal ligament was fabricated from a uniform layer of silicone impression material. The roots were then mounted in an acrylic resin to simulate the physical condition found in tooth socket. A standardized stainless steel hand spreader of the same size as the master apical file was mounted in an Instron testing machine and lateral compaction with gutta-percha and sealer was performed. The load value was recorded from the Instron testing machine. The spreader penetration depths were measured with an endodontic ruler. The data obtained were analysed statistically using anova and Student's t-tests. RESULTS: No significant difference in initial spreader load needed to condense the master cone was found amongst the four canal preparation techniques (P > 0.05). The step-back technique with Gates-Glidden drills and the hybrid technique demonstrated the least difference between the initial spreader penetration and the working length (mean 1.925 and 2.25 mm, respectively). The step-back technique without Gates-Glidden drills and the crown-down pressureless technique had the greatest difference between initial spreader penetration and the working length (mean 4.425 and 4.75 mm, respectively). CONCLUSION: The flare created by canal preparation affected spreader penetration depth, but had no effect on the spreader load.

The potential for medical informatics in the Eastern Mediterranean Region.

This article assesses the potential value of an integrated medical/ hospital information system (IMIS) for the members of the Eastern Mediterranean Region of the World Health Organization, and describes the preliminary results of a feasibility study questionnaire done in December 1989 at Salmaniya Medical Center (SMC) in the state of Bahrain.