bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum electrolyte and blood gas changes after intrathecal and intravenous bolus injections of magnesium sulphate An experimental study in a rat model
Authors: Bahar M. , Cohen M. L. , Grinshpun Y. , Datski R. , Kaufman J. , Zaidman J. L. , Nissenbaum H. , Chanimov M.
Published: April 2005

The effect of intrathecally administered magnesium sulphate on serum levels of magnesium, sodium, potassium, calcium and blood gas variables was studied in a rat model. Magnesium sulphate given intrathecally has previously been shown to produce segmental spinal blockade with no permanent neurological damage. The previous studies, however, had not investigated the possible systemic effects of the magnesium sulphate. The serum magnesium level increased significantly at 1 and 2 h after the intrathecal injection of both 6.3% and 12.6% magnesium sulphate (6.3%: 28% at 1 h, 24% at 2 h; 12.6%: 22% at 1 h, 16% at 2 h). These changes were not as great as occurred when the same dose of magnesium sulphate was administered intravenously. In all cases, the serum magnesium had returned to normal by 24 h. There were no significant changes in calcium, sodium or potassium levels, nor in arterial blood gas variables. These results show that intrathecally administered magnesium sulphate has little effect on electrolyte homeostasis.
In vitro evaluation of the effect of profound haemodilution with hydroxyethyl starch 6%, modified fluid gelatin 4% and dextran 40 10% on coagulation profile measured by thromboelastography
Authors: Mortier E. , Ongenae M. , De Baerdemaeker L. , Herregods L. , Den Blauwen N. , Van Aken J. , Rolly G.
Published: April 2005

Synthetic colloids have been implicated as a cause of coagulopathy when administered in large quantities. The effect of profound haemodilution (50%) on coagulation profile was measured in vitro by thromboelastography. Blood samples were taken from 11 ASA grade 1 patients prior to induction of anaesthesia for elective surgery. Each sample was simultaneously tested in four different preparations: undiluted blood (control sample); blood diluted with hydroxyethyl starch 6%; blood diluted with modified fluid gelatin 4%; blood diluted with dextran 40 10%. There was a significant decrease in reaction time in the preparations treated with hydroxyethyl starch 6% and modified fluid gelatin 4%, reflecting activation of initial fibrin formation. A significant increase in clot formation time was noted in the hydroxyethyl starch 6%‐treated preparations. There was also a significant decrease in clot formation rate and maximum amplitude in the hydroxyethyl starch 6% group. Clot formation time, clot formation rate and maximum amplitude did not change in the modified fluid gelatin 4% group. Profound haemodilution with dextran 40 10% exerted extreme effects on the measured variables, very often resulting in a straight line on the thromboelastography profile.
An inexpensive, self‐assembly pressure algometer
Authors: Johnson T. W. , Watson P. J.
Published: April 2005

We have developed a simple instrument for pressure algometry. It can be made easily using components found in most anaesthetic rooms. Ten students were able to make the device using written instructions. All the resulting algometers performed within 10% accuracy limits for values up to 4 kgcm−2.
Effects of cardiopulmonary bypass and hypothermia on electroencephalographic variables
Authors: Doi M. , Gajraj R. J. , Mantzaridis H. , Kenny G. N. C.
Published: April 2005

We studied the effects of hypothermia and cardiopulmonary bypass (CPB) on four depth of anaesthesia monitors; spectral edge frequency (SEF), median frequency (MF), bispectral index (BIS) and auditory evoked potential index (AEPIndex) in 12 patients during uneventful cardiac anaesthesia. Each variable was recorded simultaneously at 10 periods during anaesthesia. All four variables were not affected by the transition to CPB. During hypothermia, values of AEPIndex, MF and SEF were tightly distributed but values of BIS were very variable and overlapped with those before induction of anaesthesia. The variability decreased during rewarming. The values of AEPIndex throughout the anaesthesia never overlapped with those before induction of anaesthesia. The AEPIndex was the most stable and reliable as a depth of anaesthesia monitor among the four variables in cardiac bypass surgery.
An audit of the safety of an acute pain service
Authors: Tsui S. L. , Irwin M. G. , Wong C. M. L. , Fung S. K. Y. , Hui T. W. C. , Ng K. F. J. , Chan W. S. , O'Reagan A. M.
Published: April 2005

We audited and analysed the adverse effects and safety of postoperative pain management on 2509 consecutive patients under care of the Acute Pain Service at a tertiary referral teaching hospital over a 32‐month period. Our standard respiratory monitoring consisted of continuous pulse oximetry, hourly respiratory rate counting, sedation scoring and intermittent arterial blood gas sampling. This protocol was reliable and detected six episodes of bradypnoea, 13 of hypercapnia and 23 of oxygen desaturation occurring in 39 patients (1.8% of all spontaneously breathing patients). Two patients required naloxone injection and none had long‐term sequelae. Hypotension due to epidural bupivacaine 0.0625% and fentanyl 3.3 μg.ml−1 infusion occurred in four patients (1.2%), all with a sensory block higher than T5. They readily responded to fluid infusion and ephedrine (two patients). Postoperative nausea or vomiting occurred in 723 (28.8%) and 380 (15.1%) patients, respectively. Odds ratio analysis showed that the risk factors for postoperative nausea and vomiting were: female gender, gynaecological operations, nongeriatric patients and systemic analgesia. Postoperative nausea and vomiting decreased analgesic efficacy by discouraging the use of patient‐controlled analgesia and was regarded as equally distressing as pain. Other side‐effects included: pruritus in 182 patients; dizziness in 333 and lower limb weakness in 73 (21.2% of patients receiving epidural local anaesthetics). It is concluded that a standard monitoring and management protocol, an experienced nursing team and reliable Acute Pain Service coverage is mandatory for the safe use of modern analgesic techniques.
The site of airway irritation during induction of anaesthesia
Authors: Dashfield A. K. , Bree S. E. , Weiss A. M. , Langton J. A.
Published: April 2005

The aim of this investigation was to study the role of the nasal airway in mediating upper airway reflexes during induction of anaesthesia when the commonly used irritant inhalational anaesthetic agent enflurane is used. In a prospective randomised study, 40 ASA 1 & 2 day‐case patients undergoing body surface surgery were recruited. Following intravenous induction using propofol, 20 patients received enflurane administered via a laryngeal mask airway (LMA), the anaesthetic vapour therefore bypassing the nasal airway. In the other group, 20 patients received enflurane anaesthesia administered using a face mask, the nasal airway therefore being exposed to inhalation anaesthetic. We were unable to demonstrate any significant (p < 0.05) differences between the two groups in relation to upper airway complications (cough, breath holding, laryngeal spasm, bronchospasm and excitement). Previous work has identified the nose as a possible important reflexogenic site for upper airway reflexes in humans during anaesthesia. We have been unable to demonstrate any difference in upper airway complications when the nasal airway was included or excluded from exposure to irritant anaesthetic vapours, when administered in a clinical setting.
Convection warmers — not just hot air
Authors: Avidan M. S. , Jones N. , Ing R. , Khoosal M. , Lundgren C. , Morrell D. F.
Published: April 2005

We sought to determine whether the forced air convection warmers (nine Bair Huggers, Augustine Medical, and one Warm Touch, Mallinkrodt Medical) used in our operating theatres could be a source of microbial pathogens. Agar plates were placed directly in the air stream of the warmers. Four of these grew potentially pathogenic organisms. When the warmers were set to blow through perforated blankets, no growth occurred. Three of the warmers were swabbed and sites of colonisation were found in their hoses. After fixing a microbial filter to the end of the hose, organisms were no longer detectable. We conclude that these warming devices are a potential source of nosocomial infection. They should only be used in conjunction with perforated blankets, should have their microbial filters changed regularly and their hoses sterilised. The inclusion of a microbial filter into the nozzle of the hose could be incorporated into the design of the warmer.
Management of severe tracheal obstruction with helium/oxygen and a laryngeal mask airway
Authors: Milner Q. J. W. , Abdy S. , Allen J. G.
Published: April 2005

We report the use of Heliox administered via a laryngeal mask airway in the treatment of a 47‐year‐old woman with Gardner's syndrome who presented with severe tracheal obstruction requiring urgent tracheostomy.
Minimum alveolar concentration for halothane in children with cerebral palsy and severe mental retardation
Authors: Frei F. J. , Haemmerle M. H. , Brunner R. , Kern C.
Published: April 2005

Children with cerebral palsy and severe mental retardation who present for operation may require lower concentrations of inhalational anaesthetics than healthy children. The minimum alveolar concentration (MAC) for halothane was measured in 36 children and adolescents, aged 4–18 years, who underwent orthopaedic surgery. The control group consisted of 12 healthy children (group 1). Children with cerebral palsy and severe mental retardation were allocated to one of two groups: those taking chronic anticonvulsant medication (group 2) (n = 12) and those who did not take any drugs (group 3) (n = 12). The mean (SEM) MAC value for halothane (expressed in volume per cent) was 0.90 (0.02) for healthy children. Children with cerebral palsy had significantly lower MAC values whether they took anticonvulsant drugs or not (0.62 (0.03) and 0.71 (0.10), respectively).
Thoracic epidural anaesthesia for coronary artery bypass graft surgeryEffects on postoperative complications
Authors: Turfrey D. J. , Ray D. A. A. , Sutcliffe N. P. , Ramayya P. , Kenny G. N. C. , Scott N. B.
Published: April 2005

We have performed a retrospective analysis of the peri‐operative course of 218 consecutive patients who underwent routine coronary artery bypass graft surgery in this institution. All patients received a standardised general anaesthetic using target‐controlled infusions of alfentanil and propofol. One hundred patients also received thoracic epidural anaesthesia with bupivacaine and clonidine, started before surgery and continued for 5 days after surgery. The remaining 118 patients received target‐controlled infusion of alfentanil for analgesia for the first 24 h after surgery, followed by intravenous patient‐controlled morphine analgesia for a further 48 h. Using computerised patient medical records, we analysed the frequency of respiratory, neurological, renal, gastrointestinal, haematological and cardiovascular complications in these two groups. New arrhythmias requiring treatment occurred in 18% of the thoracic epidural anaesthesia group of patients compared with 32% of the general anaesthesia group (p = 0.02). There was also a trend towards a reduced incidence of respiratory complications in the thoracic epidural anaesthesia group. The time to tracheal extubation was decreased in the epidural group, with the tracheas of 21% of the patients being extubated immediately after surgery compared with 2% in the general anaesthesia group (p < 0.001). There were no serious neurological problems resulting from the use of thoracic epidural analgesia.
Nitrite‐induced methaemoglobinaemia – aetiology, diagnosis and treatment
Authors: Chui J. S. W. , Poon W. T. , Chan K. C. , Chan A. Y. W. , Buckley T. A.
Published: April 2005

A 41‐year‐old woman presented with the clinical features of methaemoglobinaemia after drinking Chinese herbal medicine. A life threatening methaemoglobin level of 68% was measured. Both clinical and laboratory diagnostic difficulties were encountered. The pitfalls of pulse oximeter, blood gas analysis and co‐oximeter interpretation during diagnosis and after methylene blue administration are discussed.
Effect of low dose inhaled anaesthetic agents on the ventilatory response to carbon dioxide in humans: a quantitative review
Authors: Pandit J. J.
Published: April 2005

This paper reviews published studies (identified by a Medline‐assisted search) on the effect of ≤ 0.2 minimum alveolar concentration inhaled anaesthetic agents on the hypercapnic ventilatory response in healthy subjects. Each article was examined for the anaesthetic agent used, whether CO2 was administered using a rebreathing or a steady state (step hypercapnia) technique, and subject arousal (by audiovisual stimulation or by pain). Analysis of variance was used to assess the influence of each of these factors on the standardised hypercapnic response (the hypercapnic ventilatory response in l.min−1.kPa−1 in the presence of anaesthetic, expressed as a fraction of the response without anaesthetic). There were 21 separate studies embedded within 14 published articles. When considered together, the effect of anaesthetics on the hypercapnic ventilatory response was not significant (p = 0.089). Furthermore, when each agent was considered separately, no agent alone had a significant effect on the hypercapnic response. Neither subject arousal (p = 0.396) nor the method used to induce hypercapnia (p = 0.625) had any significant influence on the response. This suggests that the hypercapnic response is more resistant to the effects of anaesthetics than the hypoxic ventilatory response. These results indicate areas for future work. It would seem important to identify the cellular mechanisms which might underlie the difference in hypercapnic and hypoxic responses, and possible ways in which subject arousal might interact in the brain with the chemoreflexes.
Appropriate cuff volumes of the Laryngeal Tube
Authors: Asai T. , Shingu K.
Published: April 2005

The manufacturer of the Laryngeal Tube (VBM, Germany) states that the cuffs should be inflated until the intracuff pressure reaches 60 cmH2O or with a certain volume of air (60 ml for the size 3 and 80 ml for size 4). We studied 100 patients to investigate this. In addition, we examined whether the patient's height or weight could be a predictor of the required volume. Following insertion of a laryngeal tube, the cuff volume at the intracuff pressure 60 cmH2O was measured. The mean (SD) volume was 62 (7.2) ml for size 3 and 84 (11.2) ml for size 4. There was a correlation between the height of the patient and the cuff volume (correlation coefficient = 0.64; p < 0.01; volume (ml) = −86.5 + 1.02 height (cm)), and between the patient's weight and the cuff volume (correlation coefficient = 0.37; p < 0.01; volume (ml) = 45.3 + 0.558 weight (kg)). The required volume for size 3 was < 60 ml in nine of 27 patients (33%), and for size, 4 < 80 ml in 20 of 73 patients (27%). Our results support the manufacturer's recommended cuff volumes, but if the cuff is inflated with these fixed volumes (60 ml and 80 ml), the cuff would be overinflated in one‐third of patients, increasing the theoretical risk of ischaemic changes to the oropharynx. Since the cuff volume is correlated with the patient's height or weight, the cuff volume should be adjusted to the patients' stature.
Paradoxical embolism through a patent foramen ovale: an unexpected complication of tracheal extubation
Authors: Turley A. J. , Thambyrajah J. , Clarke F. L. , Stewart M. J.
Published: April 2005

A 41‐year‐old male with insulin‐dependent diabetes mellitus was admitted for an elective arthroscopic release of adhesive capsulitis of his left shoulder. At the end of the surgical procedure, he appeared to regain consciousness but then became unresponsive at the time of tracheal extubation after a violent bout of coughing, developing bilateral up‐going plantar responses, decorticate posturing and abnormal pupillary reflexes. He was transferred to the intensive care unit. The following day, the patient made a full neurological recovery. Contrast echocardiography, performed using agitated saline delivered through a femoral venous line, revealed a large patent foramen ovale with evidence of right to left shunting. In the absence of risk factors for air embolism, the clinical diagnosis was one of paradoxical embolism of venous thrombus resulting in brain stem ischaemia. The patient was commenced on life‐long aspirin to minimise future embolic risk.
A comparison of direct laryngoscopy and jaw thrust to aid fibreoptic intubation*
Authors: Stacey M. R. , Rassam S. , Sivasankar R. , Hall J. E. , Latto I. P.
Published: April 2005

We compared two manoeuvres, jaw thrust and laryngoscopy, to open the airway during fibreoptic intubation in 50 patients after induction of anaesthesia in a crossover study. Patients were randomly allocated to receive either jaw thrust or conventional Macintosh laryngoscopy first. Airway clearance was assessed at both the soft palate and the epiglottis. Direct laryngoscopy provided significantly better airway clearance at the level of the soft palate than jaw thrust (44 (88%) vs 31 (62%), respectively; p = 0.002). At the level of the larynx, airway clearance was equally good in both groups (45 (90%) vs 46 (92%), respectively; p = 0.56). The times to view the larynx (median (interquartile range [range]) 4 (3–5 [2–35]) s vs 3 (3–4 [2–8]) s, respectively) and intubation time (20 (17–23 [11–83]) s vs 18 (15–20 [11–28]) s, respectively) were also similar.
The effect of high altitude commercial air travel on oxygen saturation
Authors: Humphreys S. , Deyermond R. , Bali I. , Stevenson M. , Fee J. P. H.
Published: April 2005

Air travel has increased steadily over the last decade, and its effect on the health of passengers has been the subject of much debate. There is a paucity of evidence on the effects of air travel on oxygen saturation in general populations. The peripheral oxygen saturation and pulse rate of 84 passengers, aged 1–78 years, were measured by pulse oximetry at round level and altitude during air travel. There was a statistically significant reduction in oxygen saturation in all passengers travelling long haul and short haul flights (p < 0.05). The mean [range] (SD) SpO2 for all flights at ground level was 97% [93–100] (1.33) and at cruising altitude 93% [85–98] (2.33). Fifty‐four per cent of passengers had SpO2 values of 94% or less at cruising altitude. This is a value which may prompt physicians to administer supplemental oxygen in hospital patients.
Mortality from percutaneous dilatational tracheostomy. A report of three cases*
Authors: McCormick B. , Manara A. R.
Published: April 2005

We report three deaths following percutaneous dilatational tracheostomy in a series of 1187 procedures undertaken in a single intensive care unit over a 13‐year period. All deaths were due to severe haemorrhage. The first patient died during the procedure from uncontrollable haemorrhage from the innominate vein. Delayed haemorrhage in the other two patients was caused by the tracheostomy tube eroding into the aorta in one patient and into the innominate vein in the other. In both these patients, the tracheal stoma was found at postmortem to be sited unexpectedly low. Fatal haemorrhage is a rare complication of percutaneous tracheostomy (0.25% in this series), but is probably under‐reported. While bronchoscopy is now used routinely during percutaneous tracheostomy insertion in most units, we speculate that ultrasound examination of the neck is more likely to identify major vascular structures at risk. However, whilst intuitive, there is little evidence that either bronchoscopy or ultrasound scanning reduces the incidence of complications. Magnetic resonance images of normal subjects are presented to demonstrate the anatomical relations of the trachea to major vascular structures and their variability.
Role of electrophysiological study and ablation in the management of recurrent atrial flutter associated with haemodynamic compromise in a critically ill patient
Authors: Kojodjojo P. , Kanagaratnam P. , Davies D. W. , Peters N. S. , Markides V.
Published: April 2005

Atrial flutter is a common arrhythmia. In the critical care setting, the arrhythmia may present in any patient, but it is most commonly seen in patients with impaired ventricular function, valvular disease, atrial dilatation or after cardiac surgery. We present a 68‐year‐old lady with recurrent poorly tolerated atrial flutter that was resistant to multiple pharmacological interventions and complicated by cardiogenic shock following direct current cardioversion. The flutter was successfully cured with radiofrequency ablation and was followed by an immediate improvement in her haemodynamic status. We review the management of acute atrial flutter and discuss the role of electrophysiologically guided ablation.
Management of subarachnoid haemorrhage in a non‐neurosurgical centre
Authors: Wilson S. R. , Hirsch N. P. , Appleby I.
Published: April 2005

Subarachnoid haemorrhage is a common neurological emergency, which carries a high morbidity and mortality. It is usually caused by rupture of an intracerebral aneurysm or, less commonly, an arteriovenous malformation. Although most patients present to a non‐neurosurgical hospital, they often require urgent neurosurgical or neuroradiological intervention. Whilst awaiting transfer to a neurological centre, active management of the patient must be instituted. This should include confirmation of the diagnosis with CT imaging, lumbar puncture or both, and recognition of the complications of subarachnoid haemorrhage, which include hydrocephalus, further haemorrhage and cerebral vasospasm. Medical management is directed towards maintaining adequate cerebral perfusion pressure whilst avoiding large increases in arterial blood pressure. Nimodipine therapy must be started early in an attempt to prevent cerebral vasospasm. The treatment options available at the neurological centre include surgical treatment or endovascular obliteration of the aneurysm or arteriovenous malformation.
Evaluation of a non‐invasive method of assessing opioid induced respiratory depression
Authors: Pattinson K. T. S. , Bowes M. , Wise R G. , Parkes M. J. , Morrell M. J.
Published: April 2005

Opioid induced respiratory depression is potentially fatal. The aim of this study was to validate a monitoring system that could be used to assess respiratory depression in postoperative patients. The hypercapnic ventilatory response was estimated non‐invasively in 12 volunteers. In two steps, we tested a system which delivered carbon dioxide (CO2) challenges through a venturi mask, measuring changes in ventilation with an uncalibrated respiratory inductance plethysmograph (RIP). RIP and pneumotachograph measurements of ventilation, taken at the same time during a CO2 challenge, were similar; group mean (SD), pneumotachograph 13.9 (3.5) l.min−1.kPa−1, RIP 14.3 (2.9) l.min−1.kPa−1. Bland–Altmann analysis showed the variation between these two methods was ± 5 l.min−1.kPa−1 (2 SD). Second, we confirmed that the venturi mask is suitable for delivering CO2 challenges. Despite the variability in RIP measurements, a simple multimodal respiratory monitoring system could be developed that incorporates clinical observation and non‐invasive measurement of the ventilatory response to CO2.
The effect of calcium channel blockers on outcome following the surgical treatment of phaeochromocytomas and paragangliomas
Authors: Lebuffe G. , Dosseh E. D. , Tek G. , Tytgat H. , Moreno S. , Tavernier B. , Vallet B. , Proye C. A. G.
Published: April 2005

The peri‐operative management of patients undergoing surgery for phaeochromocytoma or paraganglioma with calcium channel blockers (CCB) and their impact on postoperative morbidity and mortality were studied. The medical records of 105 patients undergoing surgery between 1991 and 2002 were analysed retrospectively. In all patients, the calcium channel blocker nicardipine was used for the peri‐operative management of haemodynamic changes. Sixty‐five patients (61.9%) showed transient intra‐operative hypertension. Systolic blood pressure (SBP) > 220 mmHg and SBP > 180 mmHg for > 10 consecutive minutes was observed in 14 (13%) and four patients (2.8%), respectively. SBP < 80 mmHg for > 10 consecutive minutes occurred in 13 patients (12.3%). Eleven patients (10.4%) developed postoperative complications and three patients died (2.8%). The median (range) ICU and hospital length of stay were, respectively, 1 (0–7) day and 10 (2–35) days. The sole use of calcium channel blockers for the peri‐operative management of phaeochromocytoma and paraganglioma resection does not prevent all haemodynamic changes; however, its use was associated with a low morbidity and mortality.
THIS ARTICLE HAS BEEN RETRACTED Physostigmine for the prevention of postanaesthetic shivering following general anaesthesia – a placebo‐controlled comparison with nefopam
Authors: Röhm K. D. , Riechmann J. , Boldt J. , Schuler S. , Suttner S. W. , Piper S. N.
Published: April 2005

Physostigmine was studied for its efficacy in the prevention of postanaesthetic shivering compared to nefopam and placebo. We studied 89 patients undergoing abdominal and urological surgery. The study was randomised and double‐blind, the patients received physostigmine 2 mg (n = 31), nefopam 10 mg (n = 30) or saline (n = 28). Haemodynamic parameters and temperature were measured at induction of anaesthesia (T0), and 5 min (T1), 15 min (T2), 30 min (T3) and 60 min (T4) after reaching the postanaesthetic care unit (PACU). Significantly less shivering occurred following administration of physostigmine and nefopam (9.7 and 3.3%) compared to placebo (53.6%). The degree of shivering was also significantly reduced following physostigmine and nefopam (p < 0.01). Extubation time, haemodynamic parameters and tympanic temperature were found to be similar in all groups. Aldrete score, duration of PACU stay and postoperative analgesic requirements did not differ between the groups. Only nefopam significantly (p < 0.01) reduced postoperative nausea and vomiting. Physostigmine is a safe alternative to nefopam, significantly reducing the incidence and severity of postanaesthetic shivering without affecting postanaesthetic recovery.
A comparison of 0.2 and 0.5 mg intrathecal morphine for postoperative analgesia after total knee replacement
Authors: Bowrey S. , Hamer J. , Bowler I. , Symonds C. , Hall J. E.
Published: April 2005

The optimal dose of intrathecal morphine for postoperative analgesia after major surgery is a matter of debate, with some uncertainty concerning the therapeutic potential and safety of intrathecal morphine in the dose range 0.3–1.0 mg. This randomised double‐blind study compared the efficacy and side‐effect profile of 0.2 mg and 0.5 mg intrathecal morphine in 70 patients undergoing knee replacement surgery. The primary endpoint was the number of patients requiring rescue analgesia (tramadol) during the first 24 h postoperatively. Secondary endpoints included consumption of tramadol and the incidence of adverse effects. Fewer patients in the 0.5‐mg group required rescue analgesia in the first 24 h than in the 0.2‐mg group (16 (48%) vs 28 (85%), respectively; p = 0.003). Median (IQR [range]) tramadol consumption was lower in the 0.5‐mg group than in the 0.2‐mg group (0 (0–100 [0–350]) mg vs 100 (50–100 [0–350]) mg, respectively; p = 0.02). The incidence of adverse effects was similar in both groups. This study has demonstrated that 0.5 mg intrathecal morphine produces better analgesia than 0.2 mg after knee replacement without any increase in side‐effects.
A comparison of intrathecal fentanyl and diamorphine as adjuncts in spinal anaesthesia for Caesarean section
Authors: Lane S. , Evans P. , Arfeen Z. , Misra U.
Published: April 2005

This randomised controlled trial examines the effects of fentanyl and diamorphine, alone and in combination, as adjuncts to spinal anaesthesia for Caesarean section. Ninety‐nine women undergoing elective Caesarean section with spinal anaesthesia using 0.5% hyperbaric bupivacaine were randomly allocated to receive fentanyl 15 μg (F), diamorphine 0.25 mg (D), or fentanyl 15 μg plus diamorphine 0.25 mg (FD), intrathecally. All women received morphine via a patient controlled analgesia system after surgery. There was no significant difference between the groups in time to achieve a block, discomfort, ephedrine use, nausea and vomiting, pruritus and sedation during surgery. Significant differences were observed in morphine consumption 4, 8, 12 and 24 h after surgery between both F and D groups, and F and FD groups, and also at 2 h between F and FD groups. There was a significant difference in pruritus at 4 h between the F and FD group. Our results suggest that diamorphine alone provides optimum benefits during and after surgery, when used in combination with hyperbaric bupivacaine for Caesarean section.
Broadband constant‐coefficient propagators
Authors: Fu Li‐Yun
Published: April 2005

The phase error between the real phase shift and the Gazdag background phase shift, due to lateral velocity variations about a reference velocity, can be decomposed into axial and paraxial phase errors. The axial phase error depends only on velocity perturbations and hence can be completely removed by the split‐step Fourier method. The paraxial phase error is a cross function of velocity perturbations and propagation angles. The cross function can be approximated with various differential operators by allowing the coefficients to vary with velocity perturbations and propagation angles. These variable‐coefficient operators require finite‐difference numerical implementation. Broadband constant‐coefficient operators may provide an efficient alternative that approximates the cross function within the split‐step framework and allows implementation using Fourier transforms alone. The resulting migration accuracy depends on the localization of the constant‐coefficient operators. A simple broadband constant‐coefficient operator has been designed and is tested with the SEG/EAEG salt model. Compared with the split‐step Fourier method that applies to either weak‐contrast media or at small propagation angles, this operator improves wavefield extrapolation for large to strong lateral heterogeneities, except within the weak‐contrast region. Incorporating the split‐step Fourier operator into a hybrid implementation can eliminate the poor performance of the broadband constant‐coefficient operator in the weak‐contrast region. This study may indicate a direction of improving the split‐step Fourier method, with little loss of efficiency, while allowing it to remain faster than more precise methods such as the Fourier finite‐difference method.
Detection of thyroglobulin mRNA as truncated isoform(s) in mouse thymus
Authors: Li Haiyan S. , Carayanniotis George
Published: April 2005

Recent studies employing reverse transription–polymerase chain reaction (RT–PCR) have demonstrated the intrathymic presence of mRNA for various autoantigens, including thyroglobulin (Tg). Deliberations on the mechanisms of central tolerance usually assume that this approach detects intact mRNA transcripts that can be translated to express the whole autoantigen in the thymus. In the present study, we tested this assumption using mRNA transcripts of mouse Tg which encode at least 13 pathogenic peptides, scattered over a large (8·5 kb) sequence. We found that mRNA encoding 11 out of these 13 Tg peptides was present in both the thyroid and the thymus of CBA/J mice, with no apparent temporal fluctuations in expression from birth to 12 weeks of age. Interestingly, detection of these sequences was also demonstrable in the liver and kidney, but not in muscle. However, mRNA encoding two pathogenic peptides (amino acids 1–12 and amino acids 1579–1591) was detected intrathyroidally but not in the other tissues. Further analysis by RT–PCR showed that Tg mRNA transcripts in the thymus, liver and kidney lack segments within the 1–915 bp and 961–5013 bp regions, spANNing exons 1–7 and 9–22, respectively. These data strongly suggest that certain known and perhaps other, as yet unmapped, pathogenic T‐cell epitopes of Tg cANNot be encoded by the truncated isoform(s) of intrathymic Tg mRNA. These findings also imply that central tolerance to endogenous Tg produced by thymic epithelial cells may be incomplete.
Modulated interaction of the ERM protein, moesin, with CD93
Authors: Zhang Mingyu , Bohlson Suzanne S. , Dy Marisela , Tenner Andrea J.
Published: April 2005

CD93 is a cell‐surface glycoprotein that has been shown to influence defence collagen‐enhanced Fc‐receptor or CR1‐mediated phagocytosis of suboptimally opsonized targets in vitro, and CD93‐deficient mice are defective in the clearance of apoptotic cells in vivo. To investigate the mechanism of CD93 modulation of phagocytic activity, GST fusion proteins containing the 47 amino acid intracellular domain (GST‐Cyto), or various mutants of the intracellular domain of CD93, were constructed and used to identify intracellular CD93‐binding molecules. The intracellular protein moesin, well characterized for its role in linking transmembrane proteins to the cytoskeleton and in cytoskeletal remodelling, bound to GST‐Cyto when either cell lysates or recombinant moesin were used as a source of interacting molecules. An association of moesin with CD93 within intact cells was confirmed by co‐capping moesin with CD93 in human monocytes. The moesin‐binding site on CD93 mapped to the first four positively charged amino acids in the juxtamembrane region of the CD93 cytoplasmic tail. Interestingly, deletion of the last 11 amino acids from the C terminus of CD93 (GST‐Cyto‐C11) dramatically increased moesin binding to the cytoplasmic tail of CD93 in the cell lysate assay, but not when the binding of purified recombinant moesin was assessed. Furthermore, moesin binding to CD93 was enhanced by the addition of phosphatidylinositol 4,5‐bisphosphate (PIP2). Taken together, these data suggest that the interaction of moesin with the CD93 cytoplasmic domain is modulated by binding of other intracellular molecules to the C11 region and implies that a PIP2 signalling pathway is involved in CD93 function.
CD4+ T‐cell responses and distribution at the colonic mucosa during Brachyspira hyodysenteriae‐induced colitis in pigs
Authors: Hontecillas Raquel , Bassaganya‐Riera Josep , Wilson Jennifer , Hutto David L. , Wannemuehler Michael J.
Published: April 2005

The spirochaete Brachyspira hyodysenteriae causes swine dysentery, a severe colitis characterized by mucosal enlargement as a result of crypt elongation and epithelial necrosis. Most efforts to understand the pathogenesis of this disease have focused on the aetiological agent and its virulence factors. However, the host immune response has been considered an important factor in disease development. Previous research has shown that B. hyodysenteriae induces systemic CD4+ and γδ T‐cell responses after intramuscular immunization. Here, we have evaluated changes in the CD4+ and γδ T‐cell composition and distribution the different compartments of the colonic mucosa of pigs challenged with B. hyodysenteriae. We report that, in infected pigs, γδ T cells were significantly depleted from the epithelial layer, although their numbers were maintained in the lamina propria. In addition, CD4+ T cells aggregated in clusters located in the lamina propria and submucosa. Ex vivo analyses of CD4+ T‐cell responses to B. hyodysenteriae antigens correlated with the changes in the mucosal CD4+ T‐cell distribution observed in infected pigs; CD4+ T cells recovered from peripheral blood and colonic lymph nodes of infected pigs proliferated to B. hyodysenteriae antigens, whereas no differences were found in the γδ T‐cell responses between challenged and control groups. In addition, colonic lymph node CD4+ T cells had a predominant memory/activated phenotype. These results indicate that infection with B. hyodysenteriae induces a mucosal CD4+ T‐cell response and points to CD4+ T cells being important contributors to the immunopathogenesis of swine dysentery.
Induction of human papillomavirus type 16‐specific immunologic responses in a normal and an human papillomavirus‐infected populations
Authors: Cheng Wen‐Fang , Lee Chien‐Nan , Su Yi‐Ning , Chang Ming‐Cheng , Hsiao Wen‐Chun , Chen Chi‐An , Hsieh Chang‐Yao
Published: April 2005

Human papillomavirus (HPV) infection, especially with the oncogenic genotypes, is the most important risk factor for developing cervical cancer. We focused on generating HPV16 E7‐specific cytotoxic CD8+ T lymphocytes and evaluating HPV16 E7‐specific immune responses in HPV16‐infected and uninfected populations. Peripheral blood mononuclear cells (PBMCs) were first collected from an uninfected group with an human lymphocyte antigen (HLA) A2 haplotype (four volunteers). Mature monocyte‐derived dendritic cells (DCs) were generated from the PBMCs and pulsed with one of two HLA‐A2‐restricted E7 peptides, aa 11–20 [YMLDLQPETT] and aa 86–93 [TLGIVCPI], as antigen presenting cells. The autologous naïve or cultured PBMCs were then cultured with peptide‐pulsed DCs to detect the HPV16 E7‐specific immune responses by a variety of techniques such as enzyme‐linked immunosorbent assay (ELISA), enzyme‐linked immunospot (ELISPOT) assay and cytotoxic T lymphocyte assay. Interferon‐γ (IFN‐γ) from E7‐specific cytotoxic CD8+ T lymphocytes stimulated with the respective peptide was detected by ELISA. Using ELISPOT analysis, a marked increase in the number of IFN‐γ‐secreting CD8+ E7‐specific lymphocytes was observed following peptide stimulation. Cultured CD8+ T lymphocytes were highly cytotoxic against the CaSki cells. PBMCs were then colleted from an HPV16‐infected population of the HLA‐A2 haplotype, including four persons of HPV16 infection only, four with cervical intraepithelial neoplasia (CIN) lesions, and four cervical cancer patients. We then compared the immunologic responses to E7 between HPV16‐infected and uninfected populations by ELISA and ELISPOT assay. The E7‐specific immunologic responses of the HPV16‐infected populations were significantly higher than those of the uninfected population. In addition, persons with an HPV16 infection only or those with CIN lesions generated higher E7‐specific immunologic responses than cervical cancer patients. Our results demonstrate methods for evaluating E7‐sepcific immunologic responses and reflect the biological responses of HPV16‐infected people during different periods of cervical disease.
Epicutaneous immunization induces αβ T‐cell receptor CD4 CD8 double‐positive non‐specific suppressor T cells that inhibit contact sensitivity via transforming growth factor‐β
Authors: Szczepanik Marian , Bryniarski Krzysztof , Tutaj Monika , Ptak Maria , Skrzeczynska Joanna , Askenase Philip W. , Ptak Wlodzimierz
Published: April 2005

Since it was previously shown that protein antigens applied epicutaneously in mice induce allergic dermatitis mediated by production of T helper 2 (Th2) cytokines we postulated that this might induce suppression of Th1 immunity. Here we show that epicutaneous immunization of normal mice with a different protein antigen applied on the skin in the form of a patch induces a state of subsequent antigen‐non‐specific unresponsiveness caused by suppressor T cells (Ts) that inhibit sensitization and elicitation of effector T‐cell responses. Suppression is transferable in vivo by αβ‐T‐cell receptor CD4+ CD8+ double positive lymphocytes harvested from lymphoid organs of skin patched animals and are not major histocompatibility complex‐restricted nor antigen specific. Both CD25+ and CD25– CD4+ CD8+ T cells are able to suppress adoptive transfer of Th1 effector cells mediating cutaneous contact sensitivity. In vivo treatment with monoclonal antibodies showed that the cytokines interleukin (IL)‐4, IL‐10 and transforming growth factor‐β (TGF‐β) are involved in the induction of the Ts cells. Additionally, using IL‐10–/– mice we found that IL‐10 is involved in skin induced tolerance. Further in vitro experiments showed that lymph node cells of skin tolerized mice non‐specifically suppress [3H]thymidine incorporation by antigen‐stimulated immune cells and this effect can be abolished by adding anti‐TGF‐β, but not anti‐IL‐4 nor anti‐IL‐10 antibodies. These studies indicate the crucial role of TGF‐β in skin induced tolerance due to non‐antigen‐specific Ts cells and also show that IL‐4, IL‐10 and TGF‐β play an important role in the induction of epicutaneously induced Ts cell suppression.
Increasing the foreignness of an antigen, by coupling a second and foreign antigen to it, increases the T helper type 2 component of the immune response to the first antigen
Authors: Ismail Nahed , Basten Antony , Briscoe Helen , Bretscher Peter A.
Published: April 2005

It has been proposed that the degree of an antigen's foreignness is important in determining the Th1/Th2 phenotype of the immune response it generates. We test this hypothesis here and partially dissect the underlying mechanism. Immunization of C57BL/6 and hen egg lysozyme (HEL)‐transgenic mice, tolerant to HEL at the T‐cell level, with low doses of sheep red blood cells (SRBC), generated a predominant T helper type 1 (Th1) response in both mouse strains. However, substantial numbers of SRBC‐specific Th2 cells were generated when normal, but not HEL‐transgenic, mice were immunized with a low dose of the conjugate HEL‐SRBC. The generation of these anti‐SRBC Th2 cells in normal mice required that HEL be coupled to SRBC, since HEL was ineffective in deviating the response to SRBC when present but coupled to another, non‐cross‐reacting, xenogeneic RBC. This Th2 deviation of the anti‐SRBC response by HEL thus requires the operational recognition of HEL epitopes linked to SRBC. Thus increasing the foreignness of an antigen increases its ability to generate Th2 cells. Our findings, in the context of previous observations in related systems, support the proposal that more CD4+ T‐cell/CD4+ T‐cell interactions, mediated by the operational recognition of linked epitopes, are required to generate Th2 cells than Th1 cells.
Cloning and characterization of equine CD89 and identification of the CD89 gene in chimpanzees and rhesus macaques
Authors: Morton H. Craig , Pleass Richard J. , Storset Anne K. , Brandtzaeg Per , Woof Jenny M.
Published: April 2005

Immunoglobulin A (IgA) is the major antibody class present in external secretions of mammals. At the vulnerable mucosal surfaces, IgA provides a crucial first‐line defence by neutralizing pathogens. Primates also have a substantial level of IgA in serum and although not well understood, the biological role of this IgA depends, at least partly, on its ability to interact with specific receptors (FcαRs) on the surface of leucocytes. The human FcαR, CD89, was the first IgA Fc receptor to be identified and binding of IgA‐coated particles to CD89 triggers numerous cellular effector functions, including phagocytosis, antibody‐dependent cellular cytotoxicity, and release of inflammatory mediators, all of which may play an important role in both systemic and mucosal immunity. For many years humans were the only species known to express CD89, however, it has recently been cloned from cows and rats. Here, we describe the identification of the CD89 gene in three additional species: horses, chimpanzees, and Rhesus macaques. Equine CD89 was identified at the cDNA level, whereas the chimpanzee and Rhesus macaque genes were identified from the available draft genomic sequence. Interestingly, when compared with humans and other primates, horses, cows and rats have a relatively low concentration of serum IgA, so the role of CD89 in these species is of particular interest. The identification and characterization of CD89 in different species will contribute to a greater understanding of the biological role of IgA and CD89 in mucosal and systemic immunity throughout evolution.
The role of macrophages in the in vitro generation of extracellular DNA from apoptotic and necrotic cells
Authors: Choi Jin‐Jung , Reich Charles F. , Pisetsky David S.
Published: April 2005

Cell death is a ubiquitous process that occurs by apoptosis or necrosis depending on the triggering event. While apoptotic and necrotic cells differ biochemically, both are cleared by macrophages for elimination. The process is very efficient, although DNA can appear in the blood in various clinical conditions associated with cell death. To define the role of macrophages in the generation of extracellular DNA, in vitro experiments were performed, assessing the release of DNA into the media of apoptotic or necrotic Jurkat cells cultured with RAW264.7 or J774 macrophage cell lines. DNA was measured by a fluorimetric assay using the dye PicoGreen. In these experiments, while necrotic cells alone did not release DNA, in the presence of macrophages, significant amounts of DNA appeared in the medium. This DNA contained sequences from the Jurkat cells and had reduced molecular weight in comparison to cellular DNA. Furthermore, coculture of macrophages with enucleated necrotic Jurkat cells did not release DNA, suggesting that the DNA came from the dead cell. In contrast, Jurkat cells made apoptotic by treatment with either staurosporine or etoposide spontaneously released DNA, while coculture with macrophages caused a decrease in the DNA released. With apoptotic cells, the DNA in the medium showed low molecular weight and laddering whether or not macrophages were present. Together, these results indicate that macrophages play an important role in the generation of extracellular DNA from dead and dying cells, with the effect dependent on how the cell died.
Neutrophil differentiated HL‐60 cells model Mac‐1 (CD11b/CD18)‐independent neutrophil transepithelial migration
Authors: Carrigan Svetlana O. , Weppler Amy L. , Issekutz Andrew C. , Stadnyk Andrew W.
Published: April 2005

During active intestinal inflammation granulocytes accumulate in the lumen of the gut where they damage the epithelium through the release of various products such as reactive oxygen species and proteolytic enzymes. Previously, using function blocking monoclonal antibodies, we showed that neutrophil migration across intestinal epithelial monolayers in response to various chemoattractants was partially β2 integrin Mac‐1 (CD11b/CD18)‐independent. Here, we show that treating neutrophils with intact monoclonal antibody (mAb) to CD18 activates the cells to express more CD11b. Thus our goal now was to determine whether neutrophil Mac‐1‐independent transepithelial migration proceeds independently of prior cell activation through Mac‐1. We took two approaches, one using blocking Fab′ fragments of mAb to CD18 and the second was to develop a neutrophil differentiated HL‐60 cell line which is Mac‐1 deficient to further study neutrophil/epithelial cell interaction. Anti‐CD18 Fab′ minimally activated neutrophils but inhibited approximately 75% of transepithelial migration to fMLP while having a minimal effect (≤25% inhibition) on the migration to C5a. Upon incubation with dimethylsulphoxide, HL‐60 cells differentiated and up‐regulated CD11b expression and migrated to C5a and n‐formyl methionyl leucyl phenylalanine in a similar manner to peripheral blood neutrophils. In contrast, CD11b expression was minimal on HL‐60 cells differentiated with dibutytyl cAMP to a neutrophil‐like phenotype. These cells, however, readily migrated across both intestinal and lung epithelial monolayers in response to C5a. We conclude that Mac‐1‐independent transepithelial migration does not require prior activation of cells via Mac‐1 ligation because HL‐60 cells lacking Mac‐1 (CD11b/CD18) expression migrate effectively. HL‐60 cells differentiated with dbcAMP should greatly assist in the search for the Mac‐1‐independent ligands for neutrophil migration across epithelium.