10 Feb 08
Posted in Genetics at 14:14 by Laci
By H Eiberg, J Troelsen, M Nielsen, A Mikkelsen, J Mengel-From, K W Kjaer and L Hansen
Hum Gen 2008;XXX:XXX-XXX
The human eye color is a quantitative trait displaying multifactorial inheritance. Several studies have shown that the OCA2 locus is the major contributor to the human eye color variation. By linkage analysis of a large Danish family, we finemapped the blue eye color locus to a 166 Kbp region within the HERC2 gene. By association analyses, we identified two SNPs within this region that were perfectly associated with the blue and brown eye colors: rs12913832 and rs1129038. Of these, rs12913832 is located 21.152 bp upstream from the OCA2 promoter in a highly conserved sequence in intron 86 of HERC2. The brown eye color allele of rs12913832 is highly conserved throughout a number of species. As shown by a Luciferase assays in cell cultures, the element significantly reduces the activity of the OCA2 promoter and electrophoretic mobility shift assays demonstrate that the two alleles bind different subsets of nuclear extracts. One single haplotype, represented by six polymorphic SNPs covering half of the 3′ end of the HERC2 gene, was found in 155 blue-eyed individuals from Denmark, and in 5 and 2 blue-eyed individuals from Turkey and Jordan, respectively. Hence, our data suggest a common founder mutation in an OCA2 inhibiting regulatory element as the cause of blue eye color in humans. In addition, an LOD score of Z = 4.21 between hair color and D14S72 was obtained in the large family, indicating that RABGGTA is a candidate gene for hair color.
Permalink
03 Feb 08
Posted in Anesthesia, Neuraxial block at 15:00 by Laci
By J. Low, N. Johnston and C. Morris
Anaethesia 2008;63:1-3
The use of epidural analgesia in patients undergoing major abdominal gastrointestinal (GIT) surgery has become routine practice. Multiple, non-randomised, small trials comparing epidural analgesia to ‘older’ opioid analgesia regimens have produced results that shaped modern practice but are rarely appropriate for modern anaesthesia. Well-structured, randomised controlled trials are few and far between and those that have been performed must be used to guide modern practice. Perceived best practice, influenced by how good the patients look in recovery, is not supported by the evidence to date. Compounding this is a lack of good evidence to accurately assess the complication rate of epidurals. The number needed to treat (NNT) and the number needed to harm (NNH) may be far closer than we think. There is a significant lack of evidence supporting the use of epidural analgesia and we question the routine use of this mode of analgesia in the postoperative period for patients having abdominal surgery. Decisions regarding the use of an epidural in any individual patient, and what we should and should not tell our patients, need to be framed from the best evidence available and not the most evidence available.
Permalink
Posted in Anesthesia, Neuraxial block at 14:55 by Laci
By J R A Rigg, K Jamrozik, P S Myles, B S Silbert, et al.
The Lancet 2002;359:1276-1282
Epidural block is widely used to manage major abdominal surgery and postoperative analgesia, but its risks and benefits are uncertain. We compared adverse outcomes in high-risk patients managed for major surgery with epidural block or alternative analgesic regimens with general anaesthesia in a multicentre randomised trial.
Methods
915 patients undergoing major abdominal surgery with one of nine defined comorbid states to identify high-risk status were randomly assigned intraoperative epidural anaesthesia and postoperative epidural analgesia for 72 h with general anaesthesia (site of epidural selected to provide optimum block) or control. The primary endpoint was death at 30 days or major postsurgical morbidity. Analysis by intention to treat involved 447 patients assigned epidural and 441 control.
Findings
255 patients (57.1%) in the epidural group and 268 (60.7%) in the control group had at least one morbidity endpoint or died (p=0.29). Mortality at 30 days was low in both groups (epidural 23 [5.1%], control 19 [4.3%], p=0.67). Only one of eight categories of morbid endpoints in individual systems (respiratory failure) occurred less frequently in patients managed with epidural techniques (23% vs 30%, p=0.02). Postoperative epidural analgesia was associated with lower pain scores during the first 3 postoperative days. There were no major adverse consequences of epidural-catheter insertion.
Interpretation
Most adverse morbid outcomes in high-risk patients undergoing major abdominal surgery are not reduced by use of combined epidural and general anaesthesia and postoperative epidural analgesia. However, the improvement in analgesia, reduction in respiratory failure, and the low risk of serious adverse consequences suggest that many high-risk patients undergoing major intra-abdominal surgery will receive substantial benefit from combined general and epidural anaesthesia intraoperatively with continuing postoperative epidural analgesia.
Permalink
