Leicester Royal Infirmary

About: Leicester Royal Infirmary is a healthcare organization based out in Leicester, United Kingdom. It is known for research contribution in the topics: Population & Carotid endarterectomy. The organization has 5300 authors who have published 6204 publications receiving 208464 citations.

Current management of postoperative nausea and vomiting.

Abstract: Before specific antiemetic agents became available, various techniques, including olive oil [51] and insulin-glucose infusions [122], were reported to be effective in reducing the incidence of postoperative nausea and vomiting (PONV). Robert Ferguson [51] described the use of olive oil in 1912. The oil was administered «by mouth immediately after partial restoration of consciousness» and he postulated that oil in the stomach «absorbed any ether that might be there»

Antimicrobial therapy to prevent or treat oral mucositis.

Abstract: Oral mucositis represents a significant source of morbidity after chemotherapy and radiation therapy. Since infection may have an important role in the pathophysiology of oral mucositis, several antimicrobial agents have been investigated for their efficacy in preventing and treating this disease. We sought to establish the weight of evidence for antimicrobial treatment and identified 31 prospectively designed clinical trials of which 13 reported some benefit and 15 did not. No clear pattern was identified regarding patient type, cancer treatment, or type of antimicrobial agent used, and inconsistent assessment of oral mucositis made comparison of outcomes difficult. Newer drugs, such as the topical antimicrobial peptide iseganan HCl initially showed promise in reducing mucositis and the related oral pain but the results of a phase 3 trial were disappointing and the line of enquiry was abandoned altogether. Hence, there is a need to better understand the role of the microflora in the cause of oral mucositis if an antimicrobial agent for prevention and treatment of this disease is to be developed.

Opioids and immune modulation: more questions than answers

Abstract: Summary 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.

Simultaneous targeting of multiple opioid receptors: a strategy to improve side-effect profile

Abstract: Opioid receptors are currently classified as µ (mu: mOP), δ (delta: dOP), κ (kappa: kOP) with a fourth related non-classical opioid receptor for nociceptin/orphainin FQ, NOP. Morphine is the current gold standard analgesic acting at MOP receptors but produces a range of variably troublesome side-effects, in particular tolerance. There is now good laboratory evidence to suggest that blocking DOP while activating MOP produces analgesia (or antinociception) without the development of tolerance. Simultaneous targeting of MOP and DOP can be accomplished by: (i) co-administering two selective drugs, (ii) administering one non-selective drug, or (iii) designing a single drug that specifically targets both receptors; a bivalent ligand. Bivalent ligands generally contain two active centres or pharmacophores that are variably separated by a chemical spacer and there are several interesting examples in the literature. For example linking the MOP agonist oxymorphone to the DOP antagonist naltrindole produces a MOP/DOP bivalent ligand that should produce analgesia with reduced tolerance. The type of response/selectivity produced depends on the pharmacophore combination (e.g. oxymorphone and naltrindole as above) and the space between them. Production and evaluation of bivalent ligands is an emerging field in drug design and for anaesthesia, analgesics that are designed not to be highly selective morphine-like (MOP) ligands represents a new avenue for the production of useful drugs for chronic (and in particular cancer) pain.