Effects of water gradients and use of urea on skin ultrastructure evaluated by confocal Raman microspectroscopy.

The rather thin outermost layer of the mammalian skin, stratum corneum (SC), is a complex biomembrane which separates the water rich inside of the body from the dry outside. The skin surface can be exposed to rather extreme variations in ambient conditions (e.g. water activity, temperature and pH), with potential effects on the barrier function. Increased understanding of how the barrier is affected by such changes is highly relevant for regulation of transdermal uptake of exogenous chemicals. In the present study we investigate the effect of hydration and the use of a well-known humectant, urea, on skin barrier ultrastructure by means of confocal Raman microspectroscopy. We also perform dynamic vapor sorption (DVS) microbalance measurements to examine the water uptake capacity of SC pretreated with urea. Based on novel Raman images, constructed from 2D spectral maps, we can distinguish large water inclusions within the skin membrane exceeding the size of fully hydrated corneocytes. We show that these inclusions contain water with spectral properties similar to that of bulk water. The results furthermore show that the ambient water activity has an important impact on the formation of these water inclusions as well as on the hydration profile across the membrane. Urea significantly increases the water uptake when present in skin, as compared to skin without urea, and it promotes formation of larger water inclusions in the tissue. The results confirm that urea can be used as a humectant to increase skin hydration.

Neuropathic agents and pain. New strategies.

At present, the opioids, anti-epileptic, membrane stabilising and anti-depressant drugs are the mainstay of treatment for alleviating neuropathic pain. This article summarises data on some new medications of these classes and also other groups of medications in development. Recent data on the use of combination medications and its implications will also be discussed.

Developing chemokine mutants with improved proteoglycan affinity and knocked-out GPCR activity as anti-inflammatory recombinant drugs.

The interaction of chemokines and GAGs (glycosaminoglycans) on endothelial surfaces is a crucial step for establishing a chemotactic gradient which leads to the functional presentation of chemokines to their GPCRs (G-protein-coupled receptors) and thus to activation of approaching leucocytes. Based on molecular modelling, biophysical investigations, cell-based and in vivo experiments, we have developed a novel concept for therapeutically interfering with chemokine-GAG interactions, namely dominant-negative chemokine mutants with improved GAG binding affinity and knocked-out GPCR activity. These recombinant proteins displace their wild-type chemokine counterparts from the natural proteoglycan co-receptors without being able to activate leucocytes via GPCRs. Our mutant chemokines therefore represent the first protein-based GAG antagonists with high therapeutic potential in inflammatory diseases.

Cardiac arrest after administration of Omnipaque radiocontrast medium during endoluminal repair of abdominal aortic aneurysm.

We describe a case of acute cardiovascular collapse in a patient with end-stage renal failure undergoing endoluminal repair of an abdominal aortic aneurysm. The 61-yr-old man suffered cardiac arrest shortly after administration of radiocontrast medium (Omnipaque), during deployment of the endovascular device. He had received the same contrast solution for diagnostic angiography on the previous day. He was successfully resuscitated and recovered completely. The differential diagnosis and management are discussed.

Dreams, images and emotions associated with propofol anaesthesia.

One hundred and twelve patients scheduled for day case varicose vein surgery were randomly allocated to one of three groups: total intravenous anaesthesia with propofol, propofol induction followed by inhalational anaesthesia with nitrous oxide and isoflurane or thiopentone induction followed by inhalational anaesthesia with nitrous oxide and isoflurane. Assessments were made in the recovery room of the incidence of dreaming, the content of the dreams and the emotional status of the patients. The groups differed significantly in reporting that they had been dreaming: patients who underwent total intravenous anaesthesia reported the most dreaming and patients who received thiopentone the least. However, despite the large number of case reports of sexual imagery following propofol anaesthesia and despite the two groups who had received propofol experiencing significantly greater happiness upon recovery than the thiopentone group, there were no appreciable differences in the sexual content of the dreams. Each group had only a small number of dreams even remotely related to sex.

Evaluation of the contribution to postoperative analgesia by local cooling of the wound.

Thirty healthy patients undergoing lumbar spine surgery were randomly assigned to one of two groups for postoperative pain relief. Group 1 received morphine via patient controlled analgesia and local cooling of the wound by an externally applied cooling pad while group 2 received patient controlled analgesia alone. There was a significant reduction in morphine consumption when local cooling was applied (18.6 mg versus 30.2 mg at 12 h, 29.0 mg versus 49.6 mg at 24 h, p < 0.05). Patients were also significantly more satisfied with their overall postoperative pain management when cooling therapy was used.

Is there any clinical advantage of increasing the pre-emptive dose of morphine or combining pre-incisional with postoperative morphine administration?

Pre-emptive treatment with an i.v. infusion of morphine 10 mg at induction reduces postoperative analgesic requirement and wound hypersensitivity compared with the same dose administered at the end of operation. Increasing the dose of preemptive morphine may potentially reduce postoperative pain further, while administering morphine at the end of operation, in addition to the beginning, may reduce pain generated by the sensory activity elicited from the wound in the immediate postoperative period. To examine this we have conducted a randomized, double-blind study in patients undergoing abdominal hysterectomy to compare the effect of morphine 20 mg administered before operation with 10 mg at induction and 10 mg on closure of the peritoneum. Postoperative pain was assessed by visual analogue score (VAS) at rest and on movement and by total morphine consumption administered by patient-controlled analgesia (PCA). Wound sensitivity was assessed by von Frey pain thresholds. Both groups had similar morphine consumption, VAS scores and touch and pain thresholds, and in both, secondary hyperalgesia was prevented. Nausea and vomiting scores were higher in the 20-mg group. There was no significant difference between the two groups and neither regimen appeared to offer obvious clinical advantages compared with a lower dose (10 mg) morphine analgesic strategy. Therefore, there may be a ceiling effect to the production of pre-emptive analgesia by morphine.