A randomized controlled trial on use of propofol alone versus propofol with midazolam, ketamine, and pentazocine "sedato-analgesic cocktail" for sedation during ERCP.

BACKGROUND AND AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) requires adequate patient sedation in order to carry out the procedure successfully. Propofol sedation is being increasingly used during ERCP. There are limited data to evaluate the efficacy of synergistic agents with propofol for sedation during ERCP. The aims of the current study were: (i) to compare patient sedation and tolerance during ERCP using either propofol alone or a "sedato-analgesic cocktail" for induction, along with propofol for maintenance, and (ii) to prospectively compare complications related to both sedation regimens. PATIENTS AND METHODS: This was a double-blind, randomized controlled trial with patients receiving either intravenous propofol alone (Group A) or a sedato-analgesic cocktail (midazolam, ketamine, and pentazocine plus propofol) (Group B) for induction; all patients received propofol for maintenance. Patient sedation and tolerance were assessed using 100-mm visual analog scales (VAS). RESULTS: A total of 199 patients undergoing ERCP were randomized (Group A, n = 104 vs. Group B, n = 95). Clinical characteristics were similar in both groups. Patient tolerance VAS scores were higher in Group B when assessed independently by both endoscopist ( P = 0.002) and anesthetist ( P = 0.001). The differences in scores occurred predominantly in younger patients. The mean propofol requirement was 192 mg in Group A and 131 mg in Group B; the mean difference was 61 mg (95%CI 40-82 mg). Patients reported equivalent levels of satisfaction with both sedation regimens. On multivariate analysis, "cocktail" use ( P = 0.013) and increasing age ( P = 0.027) significantly improved patient tolerance during ERCP. Caution during "cocktail" induction is required as transient oxygen desaturation occurs. CONCLUSION: During ERCP, propofol with a sedato-analgesic cocktail for induction results in improved patient tolerance compared with propofol alone, particularly in younger patients. Generalizations from this study to the Western world and to different cultural groups require further study.

A study into the characteristics and outcome of variceal bleeding in a tertiary hospital in Southeast Asia.

This retrospective study evaluated patients admitted to the Department of Gastroenterology, Singapore General Hospital for variceal bleeding in the year 2004. Improvement in outcome of variceal bleeding has been reported in the West. There is no regional data on this condition. This study aims to determine the characteristics and outcome of variceal bleeding in a tertiary hospital in Southeast Asia. Twenty-two patients were eligible. The main aetiologies of liver cirrhosis were chronic hepatitis B (38%) and alcohol (33%). Child's A, B and C were 29%, 48% and 24% respectively. Nineteen patients (86%) had bleeding oesophageal varices (band ligation performed). The remaining three patients (14%) had bleeding gastric varices (N-butyl-2-cyanoacrylate injection performed). Detailed description of certain endoscopic findings was absent in up to 18 patients (82%). All patients received antibiotics and vasoactive drug. In-hospital mortality and rebleeding were 9% and 18% respectively. We conclude that the relatively low in-hospital mortality and rebleeding rates in our series are most probably due to the smaller proportion of patients with severe liver dysfunction and management which adhered to recommendations. Documentation of endoscopic findings needs to be improved to facilitate the continuation of care.

Functional differences among the six Saccharomyces cerevisiae tRNATrp genes.

The Saccharomyces cerevisiae haploid genome includes six copies of the gene encoding tRNATrp which are scattered on five chromosomes. Other, non-functional tDNATrp fragments also occur in the genome. The segments of all six genes which encode the 72-nucleotide mature tRNATrp, as well as a 34-nucleotide intervening sequence, are identical. However, the 5' and 3' flanking sequences diverge virtually at the boundaries of the coding region. We have used an assay based on suppression of UGA mutations by multi-copy clones of tDNATrp to search for functional differences among these genes. Previous studies with one tDNATrp had demonstrated that moderate suppression of a UGA mutation, leu2-2, resulted from introduction of a multi-copy clone of the gene. Attempts to use this assay to select tDNATrp clones from a yeast genomic library yielded only four of the six different clones. The other two genes were amplified by PCR and cloned in pRS202, a 2 mu vector also used for the genomic library. Plasmids bearing the six tRNA genes were transformed into S. cerevisiae strain JG369.3B and scored for their ability to suppress the leu2-2 mutation as well as his4-260, another UGA marker. Two of the six tRNATrp clones were unable to suppress either marker, two evidenced weak suppression of the Leu auxotrophy, and two were able to suppress both markers. Growth rates in liquid media requiring suppression were measured for cell lines carrying each of the clones. Differences greater than 50-fold were observed in media lacking histidine. An evolutionary tree based on 5'-flanking sequence corresponds reasonably well with suppressor activity, while a similar analysis of 3'-flanking sequence does not. This suggests that the functional differences are based on divergence in the 5'-flanking sequences of the tRNATrp genes.

AFG2, an essential gene in yeast, encodes a new member of the Sec18p, Pas1p, Cdc48p, TBP-1 family of putative ATPases.

A gene from Saccharomyces cerevisiae was sequenced that encodes a protein with homology to a family of putative ATPases. These homologous proteins include the yeast cell division cycle protein Cdc48p and its mammalian homologues VCP and p97; Sec18p and its mammalian homologue NSF, proteins necessary for fusion of transport vesicles to target membranes in the secretory pathway; Pas1p, a protein necessary for peroxisome biosynthesis in yeast; Yme1p, a yeast mitochondrial protein that influences the rate of DNA escape from mitochondria; and TBP-1, MSS1 and Sug1p, proteins that interact with transcription factors. This newly sequenced gene, named AFG2 for ATPase family gene, is located on chromosome XII 5' to the SLP1/VPS33 open reading frame and encodes an essential protein of 780 amino acids that is most homologous to Cdc48p.

High-level expression of porcine fructose-1,6-bisphosphatase in Escherichia coli: purification and characterization of the enzyme.

A cDNA encoding porcine fructose-1,6-bisphosphatase was isolated from total pig liver RNA. The enzyme's coding sequence was fused to the bacteriophage T7 gene 10 promoter and transcription terminator sequence and expressed in E. coli under control of the T7 RNA polymerase. Induced cells contain elevated levels of fructose-1,6-bisphosphatase enzymatic activity and an abundant 37,000 dalton protein. The enzyme was purified to apparent homogeneity and judged identical to wild-type porcine fructose-1,6-bisphosphatase. The kinetic parameters are similar to those reported for the pig kidney enzyme. The N-terminal amino acid sequence is identical to the predicted sequence and the kinetic parameters are consistent with freedom from proteolysis. As estimated from enzymatic activity and visual inspection of coomassie blue-stained SDS-PAGE gels, porcine fructose-1,6-bisphosphatase constitutes as much as 20% of the soluble protein from the over-expressing E. coli strain.