Association of electroencephalogram trajectories during emergence from anaesthesia with delirium in the postanaesthesia care unit: an early sign of postoperative complications.

BACKGROUND: Postoperative delirium is associated with an increased risk of morbidity and mortality, especially in the elderly. Delirium in the postanaesthesia care unit (PACU) could predict adverse clinical outcomes. METHODS: We investigated a potential link between intraoperative EEG patterns and PACU delirium as well as an association of PACU delirium with perioperative outcomes, readmission and length of hospital stay. The risk factors for PACU delirium were also explored. Data were collected from 626 patients receiving general anaesthesia for procedures that would not interfere with frontal EEG recording. RESULTS: Of the 626 subjects enrolled, 125 tested positive for PACU delirium. Whilst age, renal failure, and pre-existing neurological disease were associated with PACU delirium in the univariable analysis, the multivariable analysis revealed the importance of information derived from the EEG, anaesthetic technique, anaesthesia duration, and history of stroke or neurodegenerative disease. The occurrence of EEG burst suppression during maintenance [odds ratio (OR)=1.86 (1.13-3.05)] and the type of EEG emergence trajectory may be predictive of PACU delirium. Specifically, EEG emergence trajectories lacking significant spindle power were strongly associated with PACU delirium, especially in cases that involved ketamine or nitrous oxide [OR=6.51 (3.00-14.12)]. Additionally, subjects with PACU delirium were at an increased risk for readmission [OR=2.17 (1.13-4.17)] and twice as likely to stay >6 days in the hospital. CONCLUSIONS: Specific EEG patterns were associated with PACU delirium. These findings provide valuable information regarding how the brain reacts to surgery and anaesthesia that may lead to strategies to predict PACU delirium and identify key areas of investigation for its prevention.

Frontal alpha-delta EEG does not preclude volitional response during anaesthesia: prospective cohort study of the isolated forearm technique.

BACKGROUND: The isolated forearm test (IFT) is the gold standard test of connected consciousness (awareness of the environment) during anaesthesia. The frontal alpha-delta EEG pattern (seen in slow wave sleep) is widely held to indicate anaesthetic-induced unconsciousness. A priori we proposed that one responder with the frontal alpha-delta EEG pattern would falsify this concept. METHODS: Frontal EEG was recorded in a subset of patients from three centres participating in an international multicentre study of IFT responsiveness following tracheal intubation. Raw EEG waveforms were analysed for power-frequency spectra, depth-of-anaesthesia indices, permutation entropy, slow wave activity saturation and alpha-delta amplitude-phase coupling. RESULTS: Volitional responses to verbal command occurred in six out of 90 patients. Three responses occurred immediately following intubation in patients (from Sites 1 and 2) exhibiting an alpha-delta dominant (delta power >20 dB, alpha power >10 dB) EEG pattern. The power-frequency spectra obtained during these responses were similar to those of non-responders (P>0.05) at those sites. A further three responses occurred in (Site 3) patients not exhibiting the classic alpha-delta EEG pattern; these responses occurred later relative to intubation, and in patients had been co-administered ketamine and less volatile anaesthetic compared with Site 1 and 2 patients. None of the derived depth-of-anaesthesia indices could robustly discrimate IFT responders and non-responders. CONCLUSIONS: Connected consciousness can occur in the presence of the frontal alpha-delta EEG pattern during anaesthesia. Frontal EEG parameters do not readily discriminate volitional responsiveness (a marker of connected consciousness) and unresponsiveness during anaesthesia. CLINICAL TRIAL REGISTRATION: NCT02248623.

Self-administered methoxyflurane for procedural analgesia: experience in a tertiary Australasian centre.

Methoxyflurane, an agent formerly used as a volatile anaesthetic but that has strong analgesic properties, will soon become available again in the UK and Europe in the form of a small hand-held inhaler. We describe our experience in the use of inhaled methoxyflurane for procedural analgesia within a large tertiary hospital. In a small pilot crossover study of patients undergoing burns-dressing procedures, self-administered methoxyflurane inhalation was preferred to ketamine-midazolam patient-controlled analgesia by five of eight patients. Patient and proceduralist outcomes and satisfaction were recorded from a subsequent case series of 173 minor surgical and radiological procedures in 123 patients performed using inhaled methoxyflurane. The procedures included change of dressing, minor debridement, colonoscopy and incision-and-drainage of abscess. There was a 97% success rate of methoxyflurane analgesia to facilitate these procedures. Limitations of methoxyflurane include maximal daily and weekly doses, and uncertainty regarding its safety in patients with pre-existing renal disease.

A new blood group system, RHAG: three antigens resulting from amino acid substitutions in the Rh-associated glycoprotein.

BACKGROUND AND OBJECTIVES: Rh-associated glycoprotein (RhAG) is closely associated with the Rh proteins in the red cell membrane. Two high frequency antigens (Duclos and DSLK) and one low frequency antigen (Ol(a)) have serological characteristics suggestive of expression on RhAG. MATERIALS AND METHODS: RHAG was sequenced from the DNA of one Duclos-negative, one DSLK-negative, and two Ol(a+) individuals. Recombinant protein was expressed in HEK 293 cells. Protein models with RhAG subunits were constructed. RESULTS: The original Duclos-negative patient was homozygous for RHAG 316C>G, encoding Gln106Glu. HEK 293 cells expressing Gln106Glu mutant RhAG did not react with anti-Duclos. An individual with DSLK-negative red cells was homozygous for 490A>C, encoding Lys164Gln. Two Ol(a+) members of the original Norwegian family were heterozygous for 680C>T, encoding Ser227Leu. A Japanese donor with Rh(mod) phenotype had Ol(a+) red cells and was homozygous for 680C>T. CONCLUSION: The three red cell antigens encoded by RHAG form the RHAG blood group system: Duclos is RHAG1 (030001); Ol(a) is RHAG2 (030002); and DSLK is provisionally RHAG3 (030003).

Prospective randomised clinical trial of providing patients with audiotape recordings of their oesophagogastric cancer consultations.

OBJECTIVE: To evaluate audiotape-recorded consultations at which a new diagnosis of oesophageal or gastric cancer was given to patients with reference to information retention, psychological outcome and socio-economic deprivation. METHODS: Fifty-eight patients were randomised to receive audiotaped consultations or not. Thirty-one patients received tapes (12 oesophageal and 19 gastric cancers) and were compared with 27 control patients (12 oesophageal and 15 gastric cancers). All patients were re-interviewed and completed a hospital anxiety and depression (HAD) questionnaire. Socio-economic deprivation scores were calculated using National Indices of Multiple Deprivation. RESULTS: Patients randomised to receive tapes were more likely to retain information (31 patients) than control patients (18 patients, p=0.001). Median (range) HAD scores were similar in both groups of patients [HAD A tape 6 (0-21) vs. no tape 5 (2-14), HAD D tape 3 (0-23) vs. 4 (0-10), respectively]. Deprivation correlated significantly with higher HAD A scores in control patients (p=0.039) but was not associated with information retention (p=0.667). CONCLUSION: Taped consultations were associated with significantly better information retention without adverse psychological outcomes. Providing an audiotape may reduce the effect of socio-economic deprivation on patient anxiety. PRACTICE IMPLICATIONS: Audiotaping, or its equivalent, would be a valuable tool in the multidisciplinary approach to cancers of the upper gastrointestinal tract.

The three domains of a bacterial sialidase: a beta-propeller, an immunoglobulin module and a galactose-binding jelly-roll.

BACKGROUND: Sialidases, or neuraminidases, have been implicated in the pathogenesis of many diseases, but are also produced by many non-pathogenic bacteria. Bacterial sialidases are very variable in size, often possessing domains in addition to the catalytic domain. The sialidase from the non-pathogenic soil bacterium Micromonospora viridifaciens is secreted in two forms with molecular weights of 41 kDa or 68 kDa, depending on the nature of the carbohydrate used to induce expression. RESULTS: We report here the X-ray crystal structures of the 41 kDa and 68 kDa forms of the sialidase from M. viridifaciens at 1.8 A and 2.5 A resolution respectively. In addition, we report a complex of the 41 kDa form with an inhibitor at 2.0 A resolution, and a complex of the 68 kDa form with galactose at 2.5 A. The 41 kDa form shows the canonical sialidase beta-propeller fold. The 68 kDa form possesses two additional domains, one with an immunoglobulin-like fold that serves as a linker to the second, which is homologous to the galactose-binding domain of a fungal galactose oxidase. CONCLUSIONS: The presence of the additional carbohydrate-binding domain in the 68 kDa form of the bacterial sialidase reported here is a further example of a combination of carbohydrate binding and cleaving domains which we observed in the sialidase from Vibrio cholerae. This dual function may be common, but only to other bacterial and parasitic sialidases, but also to other secreted glycosidases involved in pathogenesis. The bacterium may have acquired both the immunoglobulin module and the galactose-binding module from eukaryotes, as the enzyme shows a remarkable similarity to a fungal galactose oxidase which possesses similar domains performing different functions and assembled in a different order.

Characterization and chromosomal localization of PTP-NP-2, a new isoform of protein tyrosine phosphatase-like receptor, expressed on synaptic boutons.

Recently, there have been several reports describing the cloning and characterization of the novel family of protein tyrosine phosphatase-like receptor molecules (known as IA-2 and PTP-NP/PTP-IAR/IA-2beta/phogrin), which may act as autoantigens in diabetes. Here, we report the molecular characterization and chromosomal localization of a new isoform of this family in brain termed PTP-NP-2 (for PTP-NP tyrosine phosphatase isoform), and its function in rat primary hippocampal neurons. PTP-NP-2 has 48% identity to IA-2. The principal difference between PTP-NP-2 and PTP-NP is a 17-amino-acid insert near the N-terminus of PTP-NP that is absent in PTP-NP-2. Genomic DNA analysis indicates that the 17-amino-acid insert is coded by a separate exon, suggesting that both IA-2beta and PTP-NP-2 are isoforms arising by alternate splicing of the same gene. Reverse transcriptase-PCR revealed that both isoforms are present in human SH-SY5Y neuroblastoma cells. PTP-NP-2 mRNA expression is highly restricted, with a 5.5-kb specific transcript in human fetal and adult brain and 5.5 and 3. 8 kb in human adult pancreas. SH-SY5Y neuroblastoma and U87-MG glioblastoma cells showed specific transcripts of 5.5 and 3.8kb, respectively, indicating the existence of several isoforms of this molecule in the nervous system. The human gene encoding PTP-NP-2 was assigned to human chromosome 7q22-qter using Southern blot analysis of genomic DNAs from rodent/human somatic hybrid cell lines. Confocal microscopy analyses of rat primary hippocampal neurons revealed that PTP-NP-2 is abundantly expressed on synaptic boutons in primary neurons. Wild-type PTP-NP-2 showed no measurable tyrosine phosphatase activity using an in-vitro pNPP assay. Examination of the PTP-NP-2 catalytic consensus sequence revealed that this sequence differed from the typical tyrosine phosphatase-domain consensus sequence by an alanine to aspartate change (amino acid 930). Mutation of aspartate 930 to alanine produced a catalytically active enzyme, suggesting that native PTP-NP and its isoform PTP-NP-2 are catalytically inactive receptor protein tyrosine phosphatase homologues. Taken together, these results indicate that the tyrosine phosphatase PTP-NP-2 is a new isoform of PTP-NP tyrosine phosphatase, is expressed on synaptic boutons and may participate in the regulation of synaptic bouton endocytosis.

Effect of postoperative mydriatics on the iris.

PURPOSE: To assess the role postoperative mydriatics play after extracapsular cataract extraction (ECCE) and posterior chamber intraocular lens (IOL) implantation in causing iris modifications and in controlling inflammation. SETTING: Outpatients Department, Ninewells Hospital, Dundee, Scotland. METHODS: The prospective study comprised 136 patients who had standardized ECCE. Half the patients used a mydriatic for 2 weeks postoperatively. Anterior chamber activity, pain, and eye redness were evaluated at 2 weeks postoperatively; pupil shape, peripheral anterior synechias, IOL position, and iris adhesions, at 6 weeks. RESULTS: Iris-lens adhesions were significantly more common in the group using a mydriatic. There was no difference between the two groups in postoperative inflammation. CONCLUSION: Mydriatics should not be used routinely after ECCE with posterior chamber IOL implantation.

Novel word acquisition in children with Down syndrome: does modality make a difference?

Signing is a commonly used intervention technique for children with cognitive impairments who have expressive language delays. Novel word learning in three conditions (signed only, spoken only, signed and spoken combined) was compared for children with Down syndrome (2;1 to 5;2) and mental-age matched control children (1;4 to 2;6). Spontaneous imitations and responses to production and comprehension probes were examined after 5, 10, and 15 word exposures. No group differences in frequency of imitations or productions were obtained. The frequency of imitations was highest in the combined condition. Probed productions were infrequent, although novel words were produced most often in spoken and combined conditions. For both imitated and probed productions in the combined condition, the spoken portion was almost exclusively produced. Across conditions, children with Down syndrome comprehended fewer words than did control children. The evidence for and explanations of the facilitative effect of signs and the advantage of dual-method presentation are discussed.