Efficacy of adding clonidine to intrathecal morphine in acute postoperative pain: meta-analysis.

BACKGROUND: Clonidine may be used along with intrathecal morphine for single-dose postoperative analgesia in adults. The efficacy of this is not clear. METHODS: A meta-analysis was performed for two endpoints of efficacy: the time to first postoperative analgesia request and the amount of systemic morphine used during the first 24 h after operation. A Bayesian inference supporting direct statements about the probability of the magnitude of an effect was also used. The frequency of the five adverse events (postoperative nausea or vomiting, sedation, respiratory depression, pruritus, and hypotension) was analysed. RESULTS: Clonidine increased the duration of analgesia by 1.63 h [95% confidence interval (CI): 0.93-2.33]. There is a 90% probability that clonidine increases the duration of postoperative analgesia by more than 75 min compared with morphine alone. Clonidine reduced the amount of postoperative morphine by a mean of 4.45 mg (95% CI: 1.40-7.49 mg). There is a probability of 90% to obtain a decrease >2.3 mg but only 35% to obtain a decrease >5 mg. The incidence of hypotension was the only adverse event increased by clonidine (odds ratio 1.78; 95% CI: 1.02-3.12). CONCLUSIONS: The addition of clonidine to intrathecal morphine extends the time to first analgesia and decreases the amount of morphine used. However, as the effects are small, and the results heavily influenced by a study in which intrathecal fentanyl was also given, this must be balanced with the increased frequency of hypotension.

Bayesian enhanced meta-analysis of post-operative analgesic efficacy of additives for caudal analgesia in children.

BACKGROUND: The authors calculated the effect size for post-operative analgesia of three additives, clonidine, neostigmine, and tramadol to bupivacaine, ropivacaine, or levobupivacaine used for single-dose caudal extradural blockade in children. METHODS: A meta-analysis was performed for three end points of efficacy: the increase of time until administration of analgesic drugs, the proportion of patients requiring analgesic drugs during the initial 24 post-operative hours, and the amounts of post-operative analgesic drugs. A Bayesian inference supporting direct statements about the probability of the magnitude of an effect was used to compare the effects size. RESULTS: Neostigmine increased the duration of analgesia by 9.96 h (95% confidence interval: 7.75 to 12.16), as compared with 3.68 h (2.65 to 4.7) with clonidine and 4.45 (2.84 to 6.07) with tramadol. There is a 95% probability that neostigmine increases the duration of post-operative analgesia by more than 8 h, clonidine by more than 2.8 h, and tramadol by more than 3.25 h, as compared with local anesthetics alone. The odds ratios for the proportion of patients requiring analgesic drugs were 0.22 [0.13 to 0.37] for clonidine and 0.28 [0.10 to 0.75] for neostigmine. With tramadol, there was no statistically significant difference. All three additives reduced the amounts of post-operative analgesic drugs. Neostigmine and tramadol increase the probability for post-operative nausea or vomiting (PONV). CONCLUSIONS: Neostigmine provides the longest post-operative analgesia. With clonidine, the duration of analgesia is shorter and sedation is increased, but the probability for PONV could be decreased.

Development of a molecular probe to baboon interleukin-10 mRNA for in situ hybridization during experimental schistosomiasis.

A nucleic acid probe complementary to baboon interleukin 10 (IL-10) mRNA was developed for in situ hybridization. Highly conserved IL-10 protein sequences from several mammals were aligned to design oligonucleotide primers flanking a 270-bp sequence of the target cDNA. RNA was isolated from stimulated peripheral blood mononuclear cells (PBMC). IL-10 cDNA was reverse-transcribed from the total PBMC RNA and amplified with the polymerase chain reaction (PCR). Cloning and sequencing of the PCR product confirmed it to be of baboon IL-10 origin, with 97.8% identity to human and 100% identity to macaque mRNA sequences. The baboon IL-10 DNA probe hybridized in Southern blots to a 7.9-Kbp or 8.6-Kbp band after digestion of genomic baboon DNA with Bam H1 or Eco R1, respectively. Preliminary results with an antisense riboprobe derived from this sequence showed the presence of IL-10 mRNA in sections of granulomatous tissues.

Kinesin-II is preferentially targeted to assembling cilia and is required for ciliogenesis and normal cytokinesis in Tetrahymena.

We cloned two genes, KIN1 and KIN2, encoding kinesin-II homologues from the ciliate Tetrahymena thermophila and constructed strains lacking either KIN1 or KIN2 or both genes. Cells with a single disruption of either gene showed partly overlapping sets of defects in cell growth, motility, ciliary assembly, and thermoresistance. Deletion of both genes resulted in loss of cilia and arrests in cytokinesis. Mutant cells were unable to assemble new cilia or to maintain preexisting cilia. Double knockout cells were not viable on a standard medium but could be grown on a modified medium on which growth does not depend on phagocytosis. Double knockout cells could be rescued by transformation with a gene encoding an epitope-tagged Kin1p. In growing cells, epitope-tagged Kin1p preferentially accumulated in cilia undergoing active assembly. Kin1p was also detected in the cell body but did not show any association with the cleavage furrow. The cell division arrests observed in kinesin-II knockout cells appear to be induced by the loss of cilia and resulting cell paralysis.