Search PubMed⌕ Search

Biomedical subjects

G McGuire

Publications and source records attributed to G McGuire.

At least 19 recordsLinked to original sources

Activation of electrocorticographic activity with remifentanil and alfentanil during neurosurgical excision of epileptogenic focus.

BACKGROUND: Opioids are known to stimulate surface electroencephalographic activity in patients with temporal lobe epilepsy. The objective of the current study was to compare the electrocorticographic activation effects of the newer short-acting opioid remifentanil with those of alfentanil during epilepsy surgery under general anaesthesia. METHODS: Thirteen patients undergoing temporal lobe epilepsy surgery under general anaesthesia received alfentanil 30 microg kg(-1) and remifentanil 1 microg kg(-1) as i.v. boluses in sequence. The design was a randomized double-blind cross-over study. After opening the dura, electrocorticogram (ECoG) electrode contact strips were placed over the temporal and supratemporal neocortex and depth electrodes were inserted in the amygdala and hippocampus. Alfentanil 30 microg kg(-1) or remifentanil 1 microg kg(-1) were administered randomly in a blinded fashion. The ECoG was recorded continuously before and after the injection of each drug. The interictal epileptiform activity (spikes and sharp waves) above baseline was analysed. RESULTS: Both drugs increased epileptiform activity especially that recorded from depth electrodes in the temporal limbic structures. No epileptiform activity was recorded from the electrodes overlying the supratemporal neocortex before or after drug administration. The more potent activator was alfentanil, which caused an increase in activation from baseline of 99.8% compared with 67.4% for remifentanil. In addition, alfentanil activated the epileptiform activity in 3 patients in which remifentanil had no effect. There were no changes in heart rate after the opioid boluses. Both remifentanil and alfentanil caused significant reductions in blood pressure at 3 and 5 min after administration. CONCLUSION: We conclude that at the doses used in this study, alfentanil is the better opioid for intraoperative activation of the ECoG in neurosurgical patients undergoing resection of a temporal lobe epileptic focus. This pharmacological activation of epileptiform activity assists in localizing and confirming the site of surgical excision. Neither alfentanil nor remifentanil activated epileptiform activity in non-epileptic brain tissue.

Adult↗

Delayed diagnosis of disseminated strongyloidiasis.

We report the case of a 51-year-old woman who presented with a confusing spectrum of systemic symptoms after starting steroid therapy for a rheumatological disorder. The diagnosis of disseminated strongyloidiasis was made after a delay of 2 weeks. This paper outlines the symptom complex with which this critically ill woman presented, the course of her disease and the treatment of her disseminated strongyloidiasis.

Chronic Disease↗

Models of sequence evolution for DNA sequences containing gaps.

Most evolutionary tree estimation methods for DNA sequences ignore or inefficiently use the phylogenetic information contained within shared patterns of gaps. This is largely due to the computational difficulties in implementing models for insertions and deletions. A simple way to incorporate this information is to treat a gap as a fifth character (with the four nucleotides being the other four) and to incorporate it within a Markov model of nucleotide substitution. This idea has been dismissed in the past, since it treats a multiple-site insertion or deletion as a sequence of independent events rather than a single event. While this is true, we have found that under many circumstances it is better to incorporate gap information inadequately than to ignore it, at least for topology estimation. We propose an extension to a class of nucleotide substitution models to incorporate the gap character and show that, for data sets (both real and simulated) with short and medium gaps, these models do lead to effective use of the information contained within insertions and deletions. We also implement an ad hoc method in which the likelihood at columns containing multiple-site gaps is downweighted in order to avoid giving them undue influence. The precision of the estimated tree, assessed using Markov chain Monte Carlo techniques to find the posterior distribution over tree space, improves under these five-state models compared with standard methods which effectively ignore gaps.

Algorithms↗

TOPAL 2.0: improved detection of mosaic sequences within multiple alignments.

MOTIVATION: The Dss statistic was proposed by McGuire et al. (Mol. Biol. Evol., 14, 1125-1131, 1997) for scanning data sets for the presence of recombination, an important step in some phylogenetic analyses. The statistic, however, could not distinguish well between among-site rate variation and recombination, and had no statistical test for significant values. This paper addresses these shortfalls. RESULTS: A modification to the Dss statistic is proposed which accounts for rate variation to a large extent. A statistical test, based on parametric bootstrapping, is also suggested. AVAILABILITY: The TOPAL package (version 2) may be accessed from http:/ /www.bioss.sari.ac.uk/frank/Genetics and by anonymous ftp from typ://ftp.bioss.sari.ac.uk in the directory pub/phylogeny/topal. CONTACT: frank@bioss.sari.ac.uk

Algorithms↗

Complete upper airway obstruction during awake fibreoptic intubation in patients with unstable cervical spine fractures.

PURPOSE: To describe the presentation and management of complete upper airway obstruction with life threatening arterial oxygen desaturation that occurred during attempted awake fibreoptic intubation in two patients presenting with unstable C-spine injury. CLINICAL FEATURE: Complete upper airway obstruction occurred during awake fibreoptic intubation of two men (ASA II; 68 & 55 yr old) presenting with unstable C-spine fractures. In both cases, bag and mask ventilation with CPAP failed to relieve the progressive hypoxemia. A surgical airway was established urgently to oxygenate the two patients who were suffering progressive life-threatening oxygen desaturation. One patient had trans-cricothyroid jet ventilation performed through a 16G intravenous cannula prior to an urgent tracheostomy. In the other patient, an emergency tracheostomy was inserted. Interestingly, both patients had been sedated in the Neurosurgical Intensive Care Unit with morphine and benzodiazepines before their scheduled surgeries. The most likely etiology for the complete upper airway obstruction was laryngospasm due to inadequate topicalization of the airway and additional sedation given in the operating room. Neither patients suffered any new neurological deficits following these events. They went on to have uneventful surgeries. CONCLUSION: This case report suggest that prior to awake fibreoptic intubation, oxygenation, adequate topicalization with testing to verify the lack of pharyngeal and laryngeal responses and careful assessment of sedation levels in the operating room are prudent for a safe endoscopic intubation.

Aged↗

Improved error bounds for genetic distances from DNA sequences.

The genetic distance between two DNA sequences may be measured by the average number of nucleotide substitutions per position that has occurred since the two sequences diverged from a common ancestor. Estimates of this quantity can be derived from Markov models for the substitution process, while the variances are estimated using the delta method and confidence intervals calculated assuming normality. However, when the sampling distribution of the estimator deviates from normality, such intervals will not be accurate. For simple one-parameter models of nucleotide substitution, we propose a transformation of normal confidence intervals, which yields an almost exact approximation to the true confidence intervals of the distance estimators. To calculate confidence intervals for more complicated models, we propose the saddlepoint approximation. A simulation study shows that the saddlepoint-derived confidence intervals are a real improvement over existing methods.

Animals↗

TOPAL: recombination detection in DNA and protein sequences.

UNLABELLED: TOPAL scans a multiple sequence alignment for evidence of recombinant sequences, prior to phylogenetic analysis. AVAILABILITY: The TOPAL package may be accessed at http://www.bioss.sari.ac.uk/grainne, and by anonymous ftp at ftp.bioss. sari.ac.uk in the directory pub/phylogeny/topal. CONTACT: grainne@bioss.sari.ac.uk

Computational Biology↗

Construction of a transcription map around the gene for ataxia telangiectasia: identification of at least four novel genes.

We have constructed YAC, PAC, and cosmid contigs in the ataxia-telangiectasia gene region and used the assembled clones to isolate expressed sequences by exon trapping and hybridization selection. In the interval between D11S1819 and D11S2029, exons and cDNAs for potentially 13 different genes were identified. Three of these genes, F37, K28, and 6.82, are large novel genes expressed in a variety of different tissues. K28 shows sequence homology to the Rab GTP binding protein family and gene 6.82 homology to the rabbit vasopressin activated calcium mobilizing receptor, while gene F37 has no homology to any known sequence in the database. Three further clones, exon 6.41 and cDNAs K22 and E74, from the interval between D11S1819 and D11S2029, appear to be expressed endogenous retrovirus sequences. The fourth large novel genes, E14, together with two further possible novel genes, E13 and E3, was identified from exons and cDNAs in the more telomeric 300-kb interval between markers D11S2029 and D11S2179. These are in addition to the genes for mitochondrial acetoacetyl-CoA-acetyltransferase (ACAT) and the ATM gene in the same region. Genes E3, E13, and E14 do not show homology to any known genes. K28, 6.82, ACAT, and ATM all appear to have the same transcriptional orientation toward the telomere.

Acetyl-CoA C-Acetyltransferase↗

A graphical method for detecting recombination in phylogenetic data sets.

Current phylogenetic tree reconstruction methods assume that there is a single underlying tree topology for all sites along the sequence. The presence of mosaic sequences due to recombination violates this assumption and will cause phylogenetic methods to give misleading results due to the imposition of a single tree topology on all sites. The detection of mosaic sequences caused by recombination is therefore an important first step in phylogenetic analysis. A graphical method for the detection of recombination, based on the least squares method of phylogenetic estimation, is presented here. This method locates putative recombination breakpoints by moving a window along the sequence. The performance of the method is assessed by simulation and by its application to a real data set.

Computer Simulation↗

Upper airway edema after carotid endarterectomy: the effect of steroid administration.

The objective of this study was to evaluate the effect of preoperative steroid administration on the site and extent of upper airway edema after carotid endarterectomy. The design was a randomized, prospective, double-blind controlled trial. Thirty-eight patients undergoing elective carotid endarterectomy (17 patients were in the steroid-treated group and 21 in the control group) were administered either 16 mg of dexamethasone or saline placebo prior to surgery. Computed tomograms (CT) scans of the neck were performed on the patients preoperatively and 24 h postoperatively. Measurements were taken from the CT scans of the airway transverse and anterior-posterior diameters at the levels of the hyoid bone, arytenoid cartilage, and cricoid cartilage. No postoperative neck hematomas were seen on the CT scans. Although neck edema was observed postoperatively, the upper airway dimensions were not statistically significantly different between the steroid and the control groups. We conclude that steroid administration immediately preoperatively has no clinical effect in reducing edema formation in the upper airway postcarotid endarterectomy.

Aged↗

Evaluation of morphine versus fentanyl for postoperative analgesia after ambulatory surgical procedures.

Adequate postoperative analgesia without side effects is necessary to facilitate same-day discharge of ambulatory patients after ambulatory surgery. This study compared the use of intravenous morphine and fentanyl after painful ambulatory procedures with respect to analgesic efficacy, the incidence of side effects, and impact on the patient's readiness for discharge. Fifty-eight patients undergoing ambulatory surgery were prospectively randomized to receive morphine or fentanyl for postoperative analgesia and studied in double-blind fashion. The drugs were administered in equipotent doses in the postanesthesia care unit (PACU) and were titrated against pain scores until a visual analog score < 40 mm was achieved and the patient was satisfied with the level of analgesia. In the ambulatory surgical unit, oral analgesia was available. Pain scores, amount of analgesia used, the incidence of side-effects (nausea and vomiting, sedation and dizziness), the times to achieve recovery milestones, and fitness for discharge were studied. Equal amounts of morphine and fentanyl were used in the PACU, but pain scores were higher in the fentanyl group in the ambulatory surgical unit. In addition, the fentanyl group required more oral analgesia than the morphine group (69% vs 17%; P < 0.0002). The incidence of in-hospital side effects was similar. However, the morphine group had a more frequent incidence of postdischarge nausea and vomiting than the fentanyl group (59% vs 24%; P < 0.016). There was no significant difference in the duration of stay in the PACU (morphine vs fentanyl, 69 +/- 15 min vs 71 +/- 20 min), the times to achieve recovery milestones, and fitness for discharge (morphine vs fentanyl, 136 +/- 41 min vs 132 +/- 40 min). The short duration of fentanyl was not associated with faster discharge times; most patients required additional analgesia to control pain. Morphine produced a better quality of analgesia but was associated with an increased incidence of nausea and vomiting, the majority of which occurred after discharge.

Adult↗

Effects of varying levels of positive end-expiratory pressure on intracranial pressure and cerebral perfusion pressure.

OBJECTIVE: To determine the influence of positive end-expiratory pressure (PEEP) on intracranial pressure and cerebral perfusion pressure. DESIGN: Neurosurgical intensive care patients requiring intracranial pressure monitoring and mechanical ventilation were studied in a randomized, controlled study. SETTING: Tertiary care, neurosurgical intensive care unit. PATIENTS: Eighteen patients were enrolled in the study. Patients had posttraumatic head injuries (n = 9), subarachnoid hemorrhage (n = 7), obstructive hydrocephalus (n = 1), and intracerebral hemorrhage of unknown cause (n = 1). INTERVENTIONS: Patients had PEEP levels of 5, 10, and 15 cm H2O applied to their lungs. MEASUREMENTS AND MAIN RESULTS: Changes in intracranial pressure, mean arterial pressure, and cerebral perfusion pressure were measured. The results were analyzed separately for patients with normal and increased intracranial pressure (> 15 mm Hg). PEEP at 5 cm H2O had no effect on intracranial pressure in the group with normal intracranial pressure. However, PEEP at 10 and 15 cm H2O produced a significant (p < .05) increase in intracranial pressure (1.9 and 1.5 mm Hg, respectively). In the group with increased intracranial pressure, no significant change in intracranial pressure occurred at any of the PEEP levels used. In both groups, cerebral perfusion pressure was unchanged throughout. CONCLUSIONS: In patients with normal intracranial pressure, PEEP at 5 cm H2O did not significantly alter intracranial pressure. The clinical relevance of the intracranial pressure increase at PEEP levels of 10 and 15 cm H2O is questionable because cerebral perfusion pressure did not change and remained > 60 mm Hg. In patients with increased intracranial pressure, higher levels of PEEP did not significantly change intracranial pressure or cerebral perfusion pressure.

Adult↗

The excitability of human corticospinal neurons is depressed by thiopental.

BACKGROUND: We tested the effect of thiopental on the excitability of the corticospinal-motoneuron axis in normal human subjects. METHODS: Magnetic stimulation was used to excite the neurons in the motor cortex which give rise to the fast conducting corticospinal pathway. The characteristics of the composite excitatory post-synaptic potentials (EPSPs) produced in individual spinal motoneurons by cortical stimulation were derived from changes in the firing probability of voluntarily activated motor units of the first dorsal interosseous muscle. RESULTS: In 5 normal subjects, we found that thiopental, in incremental doses sufficient to sustain drowsiness (total dose 75 to 175 mg), significantly reduced the amplitude of these composite EPSPs. CONCLUSIONS: Thiopental reduced the facilitation of motoneurons from the cortex most likely by depressing cortical neurons.

Adult↗