Nitrous oxide withdrawal reduces intracranial pressure in the presence of pneumocephalus

Nitrous oxide anesthesia has been implicated as contributing to the development of delayed tension pneumocephalus following surgery performed in the sitting position. The authors tested the hypothesis that withdrawal of nitrous oxide anesthesia administered during formation of an intracranial gas cavity would lead to a decrease in intracranial pressure (ICP) as N2O diffuses from the cavity back into the blood. Ten halothane-anesthetized rabbits were prepared for measurement of supracortical ICP and arterial blood pressure (BP) and for intracranial volume alterations via a cisterna magna infusion catheter. Hyperventilation (Paco2 = 28-30 mmHg) and mannitol were used to shrink the brain to accommodate intracranial infusion of either air or lactated Ringer's (LR) solution, which was used to elevate ICP to between 10-15 mmHg from a baseline ICP of 2.1 +/- 2.5 mmHg over a period of 8 to 10 min. Following stabilization at an elevated ICP, inhalation of nitrous oxide (75%) was either initiated or withdrawn (if already present during the induced ICP increase) and the subsequent changes in mean ICP and BP were recorded. Following ICP elevation with LR to 10 +/- 1 mmHg, initiation of 75% N2O administration resulted in no change in ICP and modest increases (P less than 0.05) in BP and cerebral perfusion pressure (CPP = BP - ICP) after 4 min. However, when ICP was raised (to 12 +/- 3.5 mmHg) with intracranial air infusion, subsequent initiation of 75% N2O inhalation caused an abrupt ICP increase to 22.3 +/- 9 mmHg (from control P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Beta-proline analogues as agonists at the strychnine-sensitive glycine receptor.

3-Carboxy-3,4-dehydropyrrolidine was found to bind with affinity equal to that of glycine in a [3H]strychnine binding assay. Simple substitution of the 1-, 2-, 4-, or 5-position resulted in marked loss of affinity. A decline in affinity was also found upon enlargement, contraction, or saturation of the 5-membered ring. However, beta-proline and azetidine-3-carboxylic acid retained significant binding affinity. Despite its good affinity in [3H]strychnine binding, 3-carboxy-3,4-dehydropyrrolidine showed only weak agonist activity in intracellular recordings of cultured murine spinal cord neurons. This apparent lack of correlation between binding and functional results is discussed in light of the current models of the strychnine-sensitive glycine receptor.     

The active ingredient in EMDR: is it traditional exposure or dual focus of attention?

Very little is known about the mechanisms that underlie the therapeutic effectiveness of eye movement desensitization and reprocessing (EMDR). This study tested whether the content of participants' responses during EMDR is similar to that thought to be effective for traditional exposure treatments (reliving), or is more consistent with distancing, which would be expected given Shapiro's proposal of dual process of attention. The responses made by 44 participants with post‐traumatic stress disorder (PTSD) were examined during their first EMDR treatment session. An independent rater coded these responses according to whether they were consistent with reliving, distancing or focusing on material other than the primary trauma. The coding system was found to have satisfactory inter‐rater reliability. Greatest improvement on a measure of PTSD symptoms occurred when the participant processed the trauma in a more detached manner. Cross‐lagged panel correlations suggest that processing in a more detached manner was a consequence of the EMDR procedure rather than a measure that covaried with improvement. Copyright © 2006 John Wiley & Sons, Ltd.     

A diagnostic algorithm for male genital oedema

Male genital oedema can be defined as swelling or the appearance of swelling of the scrotum and/or the penile shaft and prepuce. Despite the various causes of genital oedema reported in the published work, a concise approach to the evaluation and management has not been sufficiently addressed.     

Picotamide inhibition of excess in vitro thromboxane B2 release by colorectal mucosa in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease is associated with increased mucosal release of eicosanoids. Among these, thromboxane A2 has been proposed as a possible inflammatory mediator; its suppression may be a useful therapeutic option. METHODS: Using a tissue incubation technique, we compared release of immunoreactive thromboxane B2 by colonic biopsies from patients with ulcerative colitis, Crohn's disease and controls, and assessed the inhibitory effect of picotamide, a thromboxane synthesis inhibitor-receptor antagonist, which has been widely used in Italy for management of ischaemic heart and cerebrovascular disease. RESULTS: Increased amounts of thromboxane B2 were released from biopsies from patients with active ulcerative colitis (median 238 pg/20 min/mg wet weight (interquartile range 147- 325), n = 12) and active Crohn's disease (252 (174-450), 6) compared with those from patients with quiescent ulcerative colitis (95 (61- 140), 12) or Crohn's disease (105 (57-201), 13), or controls (136 (64- 206), 8). Incubation with picotamide at concentrations between 100 microM and 1 mM reduced thromboxane B2 release (IC50 890 microM). CONCLUSION: Since increased thromboxane A2 production may have pathogenetic importance, thromboxane synthesis inhibitor-receptor antagonists such as picotamide merit therapeutic trial in the management of inflammatory bowel disease.     

Issues in the cross-national assessment of health technology.

With the growing international literature in economic evaluation and the rapid spread of new health technologies, there is a need to undertake, or at least interpret, economic evaluations on the international level. However, the ways in which cross-national differences affect the cost-effectiveness of health technologies or their evaluations have never been studied. This paper explores these issues by taking advantage of a unique situation in which the same economic evaluation of a new indication for a health technology was conducted simultaneously in four countries using an identical methodology. The study showed that if prior agreement on methods can be reached and local data applied, economic evaluations can be undertaken in a way that facilitates the extrapolation of results from country to country.     

Clinical importance,statistical significance and the assessment of economic and quality-of-life outcomes

The assessment of economic and quality-of-life outcomes of health care interventions is moving into a new era, with such assessments increasingly being made within the context of controlled clinical trials. Traditionally the measurement of many variables in economic evaluations, particularly costs, has been deterministic. In the context of clinical trials the measurement of variables is stochastic, with the standard principles of statistical inference being applied to analyse differences between treatments in terms of effectiveness. Economists participating in clinical research are therefore being called upon to specify the sample size for the economic component of the evaluation and to undertake statistical tests for differences in cost or cost-effectiveness. This paper discusses the current methodological issues surrounding stochastic measurement in clinical trials, discusses the additional issues raised by the assessment of economic and quality-of-life outcomes and specifies the challenges facing economists if they are to answer the questions now being posed about economic analysis by statisticians and clinical researchers. It is concluded that application of the standard principles of statistical inference to economic data is not straightforward and will require value judgements to be made about statistical significance and economic importance, which may differ from those already made in purely clinical studies.