Tracheal intubating conditions using propofol and remifentanil target-controlled infusion: a comparison of remifentanil EC50 for Glidescope and Macintosh.

BACKGROUND AND OBJECTIVE: The combination remifentanil-propofol was used for tracheal intubation without muscle relaxant in patients with anticipated difficult airway. Using a target-controlled infusion, we compared the remifentanil concentrations required for intubation with the Macintosh laryngoscope and the Glidescope, at a constant plasma concentration of propofol without muscle relaxant. METHODS: Sixty ASA I or II patients were randomly assigned to either the Macintosh or Glidescope group (30 per group). A target-controlled infusion of propofol was used to maintain a predetermined effect-site concentration of 3 microg ml. The target concentration of remifentanil for each patient in a group was determined by the response of the previous patient, using increments or decrements of 0.5 ng ml. Intubation was attempted at 4 min following induction to allow for equilibration between the blood and the effect site. The intubation response was graded as successful or failure by the Helbo-Hansen scoring system. The median effective concentration of remifentanil for tracheal intubation was determined using the probit regression model. RESULTS: The median effective concentration of remifentanil required for intubation with the Macintosh laryngoscope was 4.41 ng ml (3.13-5.27; 95% confidence interval) and that of the Glidescope was 5.45 ng ml (4.45-6.45; 95% confidence interval; P = 0.083). There was no difference in the total intubation scores. No patients showed signs of muscle rigidity. Arterial pressures or heart rate did not differ between the groups. CONCLUSION: There is no strong evidence that the target remifentanil concentrations required for adequate intubating conditions differed according to the technique used for intubation in the nonparalysed patient. We did not detect any major complications using this technique for either method.

Thiothalidomides: novel isosteric analogues of thalidomide with enhanced TNF-alpha inhibitory activity.

Thalidomide is being increasingly used in the clinical management of a wide spectrum of immunologically-mediated and infectious diseases, and cancers. However, the mechanisms underlying its pharmacological action are still under investigation. In this regard, oral thalidomide is clinically valuable in the treatment of erythema nodosum leprosum (ENL) and multiple myeloma and effectively reduces tumor necrosis factor-alpha (TNF-alpha) levels and angiogenesis in vivo. This contrasts with its relatively weak effects on TNF-alpha and angiogenesis in in vitro studies and implies that active metabolites contribute to its in vivo pharmacologic action and that specific analogues would be endowed with potent activity. Our focus in the structural modification of thalidomide is toward the discovery of novel isosteric active analogues. In this regard, a series of thiothalidomides and analogues were synthesized and evaluated for their TNF-alpha inhibitory activity against lipopolysacharide (LPS)-stimulated peripheral blood mononuclear cells (PBMC), This was combined with a PBMC viability assay to differentiate reductions in TNF-alpha secretion from cellular toxicity. Two isosteric analogues of thalidomide, compounds 15 and 16, that mostly reflect the parent compound, together with the simple structure, dithioglutarimide 19, potently inhibited TNF-alpha secretion, compared to thalidomide, 1. The mechanism underpinning this most likely is posttranscriptional, as each of these compounds decreased TNF-alpha mRNA stability via its 3'-UTR. The potency of 19 warrants further study and suggests that replacement of the amide carbonyl with a thiocarbonyl may be beneficial for increased TNF-alpha inhibitory action. In addition, an intact phthalimido moiety appeared to be requisite for TNF-alpha inhibitory activity.

Structure-activity relationships of tetramethylpiperidine-substituted phenazines against Mycobacterium leprae in vitro.

In a previous study of structure-activity relationships of selected phenazines against Mycobacterium leprae in vitro, compounds containing a 2,2,6,6-tetramethylpiperidine substitution at the imino nitrogen were most active. Therefore, the effect of substitution at the para positions of the phenyl and anilino groups in tetramethylpiperidine-substituted phenazines was assessed. As determined by radiorespirometry, activity in ascending order was observed in compounds substituted with hydrogens or fluorines, ethoxy groups, methyl groups, chlorines, and bromines and correlated with partition coefficients in octanol-water.